Part 1: Patient with any advanced or metastatic solid tumorXx_NEWLINE_xXPart 2A: Patient with any advanced or metastatic solid tumorXx_NEWLINE_xXPatients must have histologically confirmed epithelioid hemangioendothelioma which is metastatic or locally advanced (unresectable)Xx_NEWLINE_xXMetastatic disease or locally advanced disease that is not resectable.Xx_NEWLINE_xXMust have a histologically confirmed transitional cell carcinoma (TCC, also known as urothelial carcinoma), locally advanced or metastaticXx_NEWLINE_xXAt least 1 but not more than 5 prior systemic therapies for advanced/recurrent or progressing disease.Xx_NEWLINE_xXNo locally advanced or metastatic cancer requiring systemic therapy within 5 years prior to registration; no secondary primary lung cancer diagnosed concurrently or within 2 years prior to registrationXx_NEWLINE_xXPatients must have histologically or cytologically documented adenocarcinoma of the colon or rectum that is metastatic or locally advanced and unresectableXx_NEWLINE_xXPatients must have measurable disease that is metastatic or locally advanced and unresectable; imaging used to assess all disease per RECIST 1.1 must have been completed within 28 days prior to step 2 randomization; all disease must be assessed and documented on the Baseline Tumor Assessment FormXx_NEWLINE_xXPatients must have had at least one prior regimen of systemic chemotherapy for metastatic or locally advanced, unresectable disease; patients must have progressed following the most recent therapy; prior treatment with irinotecan is allowed; for patients that received adjuvant chemotherapy: prior treatment for metastatic disease is not required for patient who experienced disease recurrence during or within 6 months of completion of adjuvant chemotherapy; if the patient received one line of adjuvant treatment and had disease recurrence after 6 months of completing chemotherapy, patients will only be eligible after failing one additional line of chemotherapy used to treat the metastatic or locally advanced, unresectable disease; patients who have received >= 3 lines of systemic chemotherapy for metastatic or locally advanced, unresectable disease are not eligibleXx_NEWLINE_xXLocally advanced/unresectable or metastatic diseaseXx_NEWLINE_xXRe-registration: locally advanced/unresectable or metastatic diseaseXx_NEWLINE_xXPatients must have a locally advanced and unresectable or metastatic gastroenteropancreatic neuroendocrine carcinoma that is either known or suspected to be of gastrointestinal (GI) origin; primary tumors arising from the lung, gynecologic organs or prostate are not permittedXx_NEWLINE_xXLocally advanced or metastatic disease; locally advanced disease is defined as disease not amenable to local therapy such as surgery and/or radiationXx_NEWLINE_xXPatients with locally advanced, previously untreated squamous cell carcinoma of the vulvaXx_NEWLINE_xXNo prior immunotherapy for advanced/metastatic MCCXx_NEWLINE_xXNo prior chemotherapy or targeted systemic therapy for inoperable locally advanced or metastatic TNBCXx_NEWLINE_xXPhase II part: Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who have progressed following their last prior therapy, and fit into one of the following groups:Xx_NEWLINE_xXChemoradiation and/or surgery should be considered prior to study entry for those patients with locally advanced disease if those therapies are considered to be in the best interest of the patient.Xx_NEWLINE_xXLocally advanced disease as determined by endoscopic ultrasound (EUS) stage >= primary tumor (T) 3 and/or any T, lymph nodes (N)+ disease without metastatic disease (Mx)Xx_NEWLINE_xXHistologically or cytologically confirmed diagnosis of selected locally advanced or metastatic solid tumorsXx_NEWLINE_xXMust have failed at least 1 prior treatment regimen for locally advanced or metastatic disease or be intolerant to treatment or refuse standard treatmentXx_NEWLINE_xXSubjects must have histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease; locally recurrent disease must not be amenable to any local treatment with curative intent; metastatic disease must be demonstrated either radiographically or histologicallyXx_NEWLINE_xXHistological or cytological evidence of confirmed metastatic pancreatic or advanced bladder cancerXx_NEWLINE_xX3. Part B, must have a histologically or cytologically documented diagnosis of esophageal or gastric carcinoma, nasopharyngeal carcinoma (NPC), endometrial cancer, soft tissue sarcoma, or other orphan tumor who have received at least one line of standard systemic therapy for their respective tumor type in the metastatic setting with progressive locally advanced or metastatic disease that is not amenable to definitive local therapy with curative intent;Xx_NEWLINE_xXLocally advanced or metastatic HER2-positive breast cancer that has relapsed or is refractory to established therapiesXx_NEWLINE_xXDiagnosed with histologically or cytologically confirmed locally advanced/metastatic NSCLC with EGFR mutationXx_NEWLINE_xXHistologic or cytologic confirmation of a solid tumor that is advanced (metastatic, recurrent, and/or unresectable) with measurable disease and have at least 1 lesion accessible for biopsyXx_NEWLINE_xXIn the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, cholangiocarcinoma, pancreatic, colorectal) who have failed at least one prior therapy; subjects must have received, and then progressed or been intolerant to, at least 1 standard treatment regimen in the advanced or metastatic settingXx_NEWLINE_xXIn the dose expansion phase, Arm A will be open for 25 patients with pancreatic adenocarcinoma; patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have not received prior irinotecan; patients must have received at least one prior line of standard treatment for locally advanced or metastatic diseaseXx_NEWLINE_xXIn dose expansion phase, Arm B will be open for 25 patients with colorectal adenocarcinoma; patients must have histologic diagnosis and metastatic disease and have not received prior irinotecan; patients must have received at least one prior line of standard treatment for locally advanced or metastatic diseaseXx_NEWLINE_xXHistologic or cytological confirmation of a malignancy that is advanced (metastatic and/or unresectable) with measureable disease per RECIST v1.1Xx_NEWLINE_xXDisease that is unresectable, locally advanced, or metastatic (not amendable to curative therapy)Xx_NEWLINE_xXMetastatic or locally advanced angiosarcoma, treated with at least one prior systemic therapy where no standard of care curable therapy is available OR metastatic or locally advanced malignant and progressive epithelioid hemangioendothelioma (EHE)\r\n* A maximum of 5 EHE patients will be accrued on this studyXx_NEWLINE_xXDose escalation: Histologically or cytologically confirmed diagnosis of unresectable/locally advanced and/or metastatic HER2+ solid tumor malignancy and for which standard therapies are not available, are no longer effective, are not tolerated, or have been declined by the patient. Expansion cohort: Locally advanced or metastatic HER2+ solid tumors considered likely to respond to a HER2-targeted CD137 agonist (e.g. gastric/gastroesophageal/esophageal, breast, bladder).Xx_NEWLINE_xXHistological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumor that is not amenable for treatment with curative intent as follows:Xx_NEWLINE_xXPrior chemotherapy or any other investigational agents for the treatment of locally advanced or metastatic pancreatic cancerXx_NEWLINE_xXHistologically or cytologically confirmed locally advanced unresectable or metastatic adenocarcinoma of gastric or gastroesophageal junction; (for the 1L Cohort: no prior systemic therapy for the locally advanced or metastatic disease; for the 2L Cohort: disease progression during or following a first-line platinum-containing or fluoropyrimidine-containing chemotherapy regimen);Xx_NEWLINE_xXHistologically proven, locally advanced unresectable or metastatic solid tumors or hematologic malignancies for whom no approved therapy with demonstrated clinical benefit is available or standard treatment was declined.Xx_NEWLINE_xXAny patient with biopsy-proven pancreatic adenocarcinoma:\r\n* Group A: Patients with locally advanced or metastatic pancreatic adenocarcinoma who experienced a documented best response of investigator-assessed confirmed partial response (PR) or stable disease (SD) per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1\r\n* Group B: Patients with locally advanced or metastatic pancreatic adenocarcinoma who experienced progressive disease following first line chemotherapy or who are judged by the investigator as being ineligible to receive standard of care chemotherapy\r\n* Group C: Patients with potentially resectable pancreatic cancer who have completed planned preoperative neo-adjuvant chemotherapy, radiotherapy or combination chemoradiationXx_NEWLINE_xXParticipant has histological confirmation of a locally advanced or metastatic solid tumor of a type associated with Prolactin Receptor (PRLR) expression that has progressed on prior treatment, is not amenable to treatment with curative intent, and has no other therapy options known to provide clinical benefit or the subject is ineligible for such therapies.Xx_NEWLINE_xXHistologically confirmed locally advanced melanoma (pembrolizumab only), metastatic NSCLC (pembrolizumab only) locally advanced or metastatic urothelial carcinoma (atezolimumab only).Xx_NEWLINE_xXHave not received prior anti-cancer therapy for advanced or metastatic melanomaXx_NEWLINE_xXHistologically or cytologically documented locally advanced or metastatic urothelial carcinomaXx_NEWLINE_xXNo prior chemotherapy or targeted systemic therapy (including endocrine therapy) for inoperable locally advanced or metastatic TNBCXx_NEWLINE_xXPatients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, gastroesophageal junction [GEJ], cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy; patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine (dose escalation phase)Xx_NEWLINE_xXPatients with pancreatic adenocarcinoma; patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease that has failed at least one standard regimen; eight patients will participate in the paired biopsy studies; patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy; bone only lesions are not suitable for biopsy; these patients will provide informed consent for the paired biopsy study (dose expansion phase, arm A)Xx_NEWLINE_xXPatients with colorectal adenocarcinoma; patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and a fluoropyrimidine; eight patients will participate in the paired biopsy studies; patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy; bone only lesions are not suitable for biopsy; these patients will provide informed consent for the paired biopsy study (dose expansion phase, arm B)Xx_NEWLINE_xXAdvanced breast cancer with locally recurrent chest wall disease not amenable to surgical excision\r\n* Distant sites of disease are allowed\r\n* Prior radiation to the chest wall is not requiredXx_NEWLINE_xXProgressive metastatic or locally advanced or metastatic breast cancer.Xx_NEWLINE_xXSubject has a locally advanced unresectable or metastatic, relapsed and/or refractory, non-hematological malignancy for which treatment with an approved agent that is considered standard of care in the indication either does not exist or has proven ineffective.Xx_NEWLINE_xXRASMUT/BRAFMUT NSCLC: Subject must have a locally confirmed diagnosis of RAS (NRAS, KRAS, HRAS) or BRAF mutated non-small cell malignancies of the lung. Subject must have received at least 1 prior approved regimen for locally advanced or metastatic disease followed by documented progressive disease.Xx_NEWLINE_xXSCCHN: Subject must have a locally confirmed diagnosis of SCCHN. Subject must have received at least 1 prior approved agent for advanced or metastatic disease followed by documented progressive disease.Xx_NEWLINE_xXLocally advanced unresectable or metastatic disease that has progressed since last treatment.Xx_NEWLINE_xXHistologically or cytologically confirmed adenocarcinoma of the breast with unresectable locally advanced disease, or metastatic disease and HER2 IHC 1+ or 2+ ORXx_NEWLINE_xXHistologically or cytologically confirmed adenocarcinoma of the breast with unresectable locally advanced disease, or metastatic disease and HER2 IHC 3+ or positive for HER2 gene amplificationXx_NEWLINE_xXHistological or cytological diagnosis of metastatic cancer or locally advanced cancer that is not amenable to local therapyXx_NEWLINE_xXSubject must have locally advanced or metastatic solid tumor with no additional therapy options available that are known to provide clinical benefit per institutional standards;Xx_NEWLINE_xXDiagnosed with advanced or metastatic malignancyXx_NEWLINE_xXLocally advanced, unresectable or metastatic diseaseXx_NEWLINE_xXFor dose escalation for all combinations: The participant must have histological or cytological evidence of cancer, either a solid tumor or a lymphoma, which is advanced or metastatic.Xx_NEWLINE_xXFor Part E dose confirmation: All participants must have histological evidence of locally advanced or metastatic triple negative breast cancer (TNBC) and prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway. Participants must not have received >2 lines of systemic treatment for advanced or metastatic TNBC.Xx_NEWLINE_xXPatients with confirmed advanced hematological malignanciesXx_NEWLINE_xXPathologically-confirmed, locally advanced or metastatic solid tumors that have relapsed or are refractory to or are not considered medically suitable to receive standard of care treatment (Dose Escalation Phase)Xx_NEWLINE_xXPatients with only non-measurable bone lesions must have disease progression based on PCWG3 with 2 or more new lesions or have prostate-specific antigen (PSA) progression before enrollment. Arm 4: Patients with extensive-stage disease small cell lung cancer (SCLC) must meet the following criterion: i. Patients received ? 2 prior lines of therapy. Arm 5: Patients with HER2-negative gastric or gastroesophageal junction cancer must meet the following criterion: i. Patients received ? 2 prior lines of therapy. Arm 6: Patients with locally advanced or metastatic urothelial (muscle-invasive bladder, ureter, urethra or renal pelvis) cancer must meet the following criterion: i. Patients received ? 2 prior lines of therapy in the advanced or metastatic disease setting. ii. Patients must have received prior platinum-based systemic chemotherapy. Arm 7: Patients with advanced or metastatic pancreatic adenocarcinoma must meet the following criteria: i. Patients must have received at least one line of platinum containing regimens in either an advanced or metastatic setting, unless the patient has known deleterious germline or somatic BRCA1/2 mutation prior to being screened (in which case they can be considered for the study if the patient has never received platinum-containing regimen), AND ii. Patients received ? 1 prior lines of therapy in the advanced or metastatic disease setting. Arm 8: Patients with advanced or metastatic solid tumor malignancies must meet the following criterion: i. Patients with at least 1 prior platinum-containing treatment in any treatment setting.Xx_NEWLINE_xXFor Part C exclusively (RO6874281 in combination with cetuximab), participants with metastatic or recurrent or locally advanced squamous cell carcinoma of head and neck who have progressed on cetuximab maintenance therapy after cetuximab-containing chemotherapy or radiation therapyXx_NEWLINE_xXAll subjects must have previously treated either locally advanced or metastatic renal or urothelial cell carcinoma to be eligible for participationXx_NEWLINE_xXSubjects must have a diagnosis of measurable advanced or metastatic hepatocellular carcinoma; advanced HCC is defined as disease not amenable to surgery, ablation, transplant, or embolic therapyXx_NEWLINE_xXMetastatic disease or locally advanced, unresectable diseaseXx_NEWLINE_xXPatients with locally advanced HCC not eligible for curative therapiesXx_NEWLINE_xXLocally advanced or metastatic NSCLCXx_NEWLINE_xXHas histologically or cytologically confirmed metastatic, or unresectable locally advanced, recurrent NSCLC.Xx_NEWLINE_xXHistologically-confirmed diagnosis of advanced (unresectable Stage III) or metastatic (Stage IV) melanoma excluding mucosal, or ocular melanoma (or a histologically or cytologically-documented locally-advanced or metastatic solid malignancy in Parts 4 and 5)Xx_NEWLINE_xXPatient with histological proven metastatic GIST or non-operable locally advanced GISTXx_NEWLINE_xXRelapsed, locally-advanced or metastatic colorectal or pancreatic cancer, squamous NSCLC, or SCCHN patients who are not candidates for standard therapy.Xx_NEWLINE_xXPatients with NSCLC must have predominant squamous histology. Patients must have received prior therapy with a platinum-based treatment and a checkpoint inhibitor (CPI), if eligible, and should have received no more than 2 systemic regimens in the locally advanced or metastatic setting.Xx_NEWLINE_xXHistologic or cytologic confirmation of an incurable solid malignancy that is advanced (metastatic and/or unresectable), with measurable disease per RECIST v1.1Xx_NEWLINE_xXHistologic or cytologic confirmation of a solid tumor that is advanced (metastatic, recurrent, and/or unresectable) with measurable disease and have at least 1 lesion accessible for biopsyXx_NEWLINE_xXRefractory or intolerant to at least one prior standard therapy(ies) for metastatic or locally advanced disease.Xx_NEWLINE_xXDuring Phase 1, subjects with locally advanced or metastatic solid tumors with disease progression on or after treatment with available therapies, or who are intolerant to treatment, or who refuse standard treatment.Xx_NEWLINE_xXHistologically or cytologically confirmed locally advanced or metastatic Triple Negative Breast Cancer.Xx_NEWLINE_xXAdvanced disease is defined as metastatic disease or locally advanced disease that is not amenable to surgery or radiotherapy with curative intentXx_NEWLINE_xXPart B: Subjects must have one of the histologically- or cytologically-confirmed unresectable (locally advanced or metastatic) solid malignancies listed below, AND have measurable disease at study entry defined by RECIST 1.1. AND be considered suitable for treatment with pembrolizumab; in this study pembrolizumab will be considered an investigational study drug.Xx_NEWLINE_xXPatients must have a histologically confirmed metastatic and/or locally advanced sarcoma by the enrolling institution.Xx_NEWLINE_xXPrior therapy for breast cancer in the advanced/metastatic setting must have included at least:Xx_NEWLINE_xXDocumented evidence of advanced RCCXx_NEWLINE_xXHistopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ) adenocarcinoma that is metastatic or locally advanced and unresectableXx_NEWLINE_xXCohort 5: Prior treatment with fulvestrant; Prior treatment with chemotherapy for advanced/metastatic disease; Any line(s) of therapy following treatment failure with a CDK 4/6 inhibitor in combination with an AI; Prior treatment with chemotherapy in the advanced/metastatic setting or with fulvestrant; Advanced/metastatic disease that is symptomatic and/or with visceral spreadXx_NEWLINE_xXHistologic documentation of locally advanced, recurrent or metastatic solid malignancy that has progressed and standard therapy has been ineffective or intolerable. Phase 1b subjects must also have experienced disease progression after treatment with an anti PD-1 or PDL-1 agent.Xx_NEWLINE_xXPatients must have locally advanced, metastatic or refractory leiomyosarcoma or dedifferentiated liposarcomaXx_NEWLINE_xXhistologic or cytologic confirmation of a solid tumor that is advanced (metastatic, recurrent and/or unresectable)Xx_NEWLINE_xXPROCUREMENT INCLUSION CRITERIA: Any breast cancer patient with metastatic or locally recurrent unresectable diseaseXx_NEWLINE_xXDuring dose escalation only, an additional population with unresectable advanced and/or metastatic 2nd line RCC patients is allowedXx_NEWLINE_xXHistologically proven, locally advanced unresectable or metastatic solid tumors for whom no approved therapy with demonstrated clinical benefit is available or standard treatment was declined.Xx_NEWLINE_xXParticipants must have histologically or cytologically confirmed invasive breast cancer, with either locally advanced or metastatic disease; patients without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluationXx_NEWLINE_xXPatient with advanced or metastatic solid tumor and has disease progression or treatment intolerance after treatment with available therapiesXx_NEWLINE_xXPatients must have metastatic disease or locally advanced unresectable diseaseXx_NEWLINE_xXPathologically confirmed diagnosis of breast cancer with radiographic evidence of incurable, unresectable, locally advanced or metastatic disease (LA/MBC)Xx_NEWLINE_xXAdvanced melanoma or PD-L1-positive advanced, relapsed, or refractory solid tumor or lymphomaXx_NEWLINE_xXCohort B: Patients with histologically confirmed locally advanced or metastatic clear cell renal cell caricnoma (with clear cell component on pathology), who have been treated with at least one prior systemic therapy for locally advanced or metastatic disease, including either tyrosine kinase inhibitor and/or immune checkpoint inhibitor, with evidence of SETD2 mutation on CLIA-certified next generation sequencing panel\r\n* All next generation sequencing (NGS) sequencing reports including information pertaining to mutant allele frequency and chromosome 3p loss will be reviewed by the University of California at San Francisco (UCSF) Molecular Tumor Board to verify bi-allelic loss of SETD2Xx_NEWLINE_xXNo prior systemic therapy in the metastatic or advanced settingXx_NEWLINE_xXDisease must be locally advanced and unresectable or metastatic; disease which may be resected but with an associated level of morbidity deemed unacceptable by the treating clinician is considered eligibleXx_NEWLINE_xXHas a diagnosis of locally advanced or metastatic solid tumorXx_NEWLINE_xXPts with NSCLC must have ALK wild-type, EGFR wild-type, and ROS1 fusion negative Part 3: Locally advanced (unresectable) and/or metastatic cancer as follows:Xx_NEWLINE_xXHave advanced or metastatic cancer (solid tumors) and be an appropriate candidate for experimental therapy.Xx_NEWLINE_xXPart C: Have advanced unresectable cancer (dose escalation) and advanced/unresectable/metastatic NSCLC carrying BRAF or RAS mutation and colorectal cancer carrying RAS mutation (dose expansion)Xx_NEWLINE_xXConfirmed diagnosis of borderline resectable or locally advanced pancreatic adenocarcinomaXx_NEWLINE_xXLocally advanced unresectable or metastatic stage 4 (i.e. T4 or N3 or M1) penile squamous cell carcinoma (PSCC)Xx_NEWLINE_xXPatients must have histologically or cytologically documented carcinoma primary to the intra- or extra-hepatic biliary system or gall bladder with clinical and/or radiologic evidence of unresectable, locally advanced or metastatic disease; patients with ampullary carcinoma are not eligibleXx_NEWLINE_xXadvanced pancreatic cancerXx_NEWLINE_xXPatients with advanced or metastatic solid tumors who have disease progression after treatment with available therapies and for whom nab-paclitaxel treatment is appropriate.Xx_NEWLINE_xXAdvanced solid tumorsXx_NEWLINE_xXPatients must have advanced or metastatic NSCLC with histological or cytological confirmation. Patients with known EGFR-activating mutations or ALK rearrangements are excluded.Xx_NEWLINE_xXThe patient must have advanced disease, defined as cancer that is either metastatic, OR locally advanced and unresectable (and for which additional radiation therapy or other locoregional therapies are not considered feasible).Xx_NEWLINE_xXDose escalation:\r\n* Any locally advanced or metastatic solid tumor malignancy with no curative treatment options availableXx_NEWLINE_xXPatients may have received any number of lines of prior systemic therapy for locally advanced/metastatic diseaseXx_NEWLINE_xXPatients with metastatic (lymph node or distant metastasis, i.e. N+ or M1) or locally advanced unresectable PSCCXx_NEWLINE_xXPatients with metastatic (lymph node or distant metastasis, i.e. N+ or M1) or locally advanced unresectable (T4b) TCCXx_NEWLINE_xXPHASE IB: Histologically confirmed refractory locally-advanced unresectable or metastatic pancreatic or biliary cancerXx_NEWLINE_xXPHASE IB: =< 2 lines of prior systemic therapy for patients with progressive locally-advanced diseaseXx_NEWLINE_xXStage IIIB or IV NSCLC or relapsed locally advanced or metastatic NSCLCXx_NEWLINE_xXLocally advanced disease must not be amenable to resection with curative intentXx_NEWLINE_xXAny prior chemotherapy, hormonal, or targeted therapy, for inoperable locally advanced or metastatic triple-negative breast cancer (mTNBC)Xx_NEWLINE_xXConfirmed advanced hematologic malignancies; Phase 1:Xx_NEWLINE_xXPatients must have locally advanced or metastatic urothelial cancer that is not amenable to surgical treatmentXx_NEWLINE_xXPatient has only locally advanced disease.Xx_NEWLINE_xXPatients must have pathologically?confirmed, non-metastatic locally/regionally advanced squamous cell carcinoma of the head and neck, stage III/IV, referred for definitive chemo?RT, and meet one of the following criteria:\r\n* Primary tumor (T4) with or without metastatic lymph nodes; tumor or nodes are: unresectable, resection is considered by the treating surgeon or patient to result in unacceptable functional or oncological results, patient refuses surgery, or surgery is not possible due to co-morbidities\r\n* Human papillomavirus (HPV)(?) or p16(-) locally/regionally advanced (T3?4 or N2?3) oropharyngeal cancer\r\n* HPV(+) or p16(+) locally/regionally advanced (T4 or N3) oropharyngeal cancer\r\n* T3 or T4 laryngeal or hypopharyngeal cancer that is locally advanced, bulky (> 40 cc), unresectable, or patient declines surgery\r\n* Stage III/IV oral cavity or paranasal sinus cancers in patients who refuse surgery or are unfit for surgery\r\n* Locally/regionally advanced (stage T3?4 and/or N3) nasopharyngeal cancer which is EBV (-) (Epstein?Barr virus)Xx_NEWLINE_xXPatients with advanced and/or metastatic, histologically documented solid tumors.Xx_NEWLINE_xXPatients must have histologically confirmed malignancy confirmed by the Laboratory of Pathology, National Cancer Institute (NCI), that is metastatic or unresectable locally advanced solid epithelial or mesenchymal tumorsXx_NEWLINE_xXAdvanced myelofibrosisXx_NEWLINE_xXPhase 1: Patients with histologically or cytologically confirmed locally advanced (unresectable) or metastatic solid tumors and with progressive disease during or after treatment with a PD-1 or PD-L1-inhibitor who meet one of the following criteria:Xx_NEWLINE_xXCohort C: advanced or metastatic (stage 4) RCCXx_NEWLINE_xXLocally advanced or metastatic disease\r\n* Patients with locally advanced or metastatic disease must have disease deemed not amenable to surgical and/or locoregional therapies or patients who have progressed following surgical and/or locoregional therapies\r\n* Measurable disease, as defined as lesions that can accurately be measured in at least one dimension according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at least 1 cm with contrast enhanced dynamic imaging (magnetic resonance imaging or computed tomography)Xx_NEWLINE_xXSign of locally advanced disease or metastatic bladder cancerXx_NEWLINE_xXHave histologically or cytologically documented locally advanced unresectable or metastatic/recurrent urothelial carcinoma (including renal pelvis, ureters, urinary bladder, and urethra);Xx_NEWLINE_xXFor Cohort B: No prior chemotherapy for inoperable locally advanced or metastatic or recurrent UCa and ineligible (\unfit\) for cisplatin-based chemotherapy;Xx_NEWLINE_xXDocumented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic; patients with documented lymphomas.Xx_NEWLINE_xXHave newly diagnosed localized or locally advanced (T1N1-3M0 or T2-3NanyM0), potentially resectable disease without any prior systemic chemotherapyXx_NEWLINE_xXLocally advanced/unresectable or metastatic disease.Xx_NEWLINE_xXPatients must have had disease progression on or following their most recent treatment regimen or on presentation for the first time with locally advanced unresectable or metastatic diseaseXx_NEWLINE_xXHave histologically or cytologically-documented diagnosis of advanced (metastatic and/or unresectable) thymic carcinoma, for which no curative treatment (including surgery, radiation, or other) is availableXx_NEWLINE_xXHistologically documented, locally advanced (T4b, any N; or any T, N 2?3) or metastatic urothelial carcinoma (mUC) (M1, stage IV) (also termed TCC or UCC of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra). Patients with mixed histologies are required to have a dominant transitional cell pattern. Locally advanced bladder cancer must be inoperable on the basis of involvement of pelvic sidewall or adjacent viscera (clinical stage T4b) or bulky nodal metastasis (N2?N3)Xx_NEWLINE_xXLocally advanced or metastatic BC that has relapsed or is refractory to established therapies HER2-Expressing Gastric/Gastroesophageal (GEJ) Cancer-Specific Inclusion CriteriaXx_NEWLINE_xXAdenocarcinoma of the stomach or GEJ with inoperable locally advanced or recurrent and/or metastatic disease, not amenable to curative therapyXx_NEWLINE_xXDiagnosis of advanced or metastatic cancer not amenable to curative therapyXx_NEWLINE_xXHistologic or cytologic diagnosis of unresectable, locally advanced and/or metastatic hepatocellular carcinoma (HCC) not amenable to curative surgery, transplantation, or ablative therapies based upon assessment of treating investigatorXx_NEWLINE_xXSubjects with cytologically or histologically confirmed locally advanced or metastatic HPV associated malignancies including:\r\n* Non-neuroendocrine cervical cancers\r\n* P16+ oropharyngeal cancers\r\n* Anal cancers\r\n* Vulvar, vaginal, penile, squamous cell rectal and neuroendocrine cervical cancers\r\n* Other locally advanced or metastatic solid tumors (e.g. lung, esophagus) that are known HPV+Xx_NEWLINE_xXFor the dose expansion phase: Patients with locally advanced unresectable or metastatic, non-small cell lung cancer (NSCLC), castration-resistant prostate cancer (CRPC) and pancreatic ductal adenocarcinoma (PDAC)Xx_NEWLINE_xXDiagnosed with (a) locally advanced or metastatic (stage III-IV) breast cancer or (b) advanced prostate cancerXx_NEWLINE_xXParts B of the study will include patients with histological or cytological confirmation diagnosis of locally advanced or metastatic Stage IV NSCLC.Xx_NEWLINE_xXPart C of the study will include patients with histological or cytological confirmation diagnosis of locally advanced or metastatic Stage IV 1st-line NSCLC (for which the patient has not received therapy).Xx_NEWLINE_xXHistologically confirmed metastatic or unresectable locally advanced non-squamous NSCLC with documented EGFR mutation-positive diseaseXx_NEWLINE_xXSubjects must have a histologically confirmed metastatic and/or locally advanced sarcomaXx_NEWLINE_xXOne of the following advanced solid malignancies** which qualifies for standard of care pembrolizumab treatment per Food and Drug Administration (FDA) approval:\r\n* Locally advanced or metastatic urothelial carcinoma that has progressed during or following platinum-based chemotherapy or within 12 months of neoadjuvant/adjuvant platinum-based therapy, ONLY in the second- or later-line setting\r\n* Unresectable or metastatic MSI-H or dMMR solid tumors that have progressed during or following prior treatment and have no satisfactory alternative treatment options (including MSI-H or dMMR colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan)\r\n* Recurrent locally advanced or metastatic, gastric or gastroesophageal junction (GEJ) adenocarcinoma expressing PD-L1 (as determined by an FDA-approved test) that have progressed on or after two or more systemic therapies, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2/neu-targeted therapy\r\n**Patients who, due to the MSI-H or dMMR status of their disease, qualify for enrollment in more than one cohort (e.g. patients with MSI-H gastric adenocarcinoma) will be enrolled in the MSI-H/dMMR cohortXx_NEWLINE_xXHas a pathologically documented unresectable advanced NSCLC disease not amenable to curative therapyXx_NEWLINE_xXHistologic or cytologic confirmation of a solid tumor that is advanced (metastatic, recurrent and/or unresectable) with measurable disease per RECIST v1.1Xx_NEWLINE_xXHave histologically confirmed, locally advanced unresectable or metastatic (stage IV) colorectal adenocarcinomaXx_NEWLINE_xXPatients with inflammatory breast cancer, widespread locally advanced unresectable disease involving the chest wall/nodal basins in which a curative surgical resection cannot be performed, or those in whom de novo metastatic disease is suspected or confirmedXx_NEWLINE_xXHistologically confirmed locally advanced and unresectable or metastatic melanomaXx_NEWLINE_xXHistologically confirmed diagnosis of metastatic or locally advanced unresectable tumorsXx_NEWLINE_xXMore than 1 line of prior chemotherapy in the treatment of metastatic or locally advanced/recurrent disease.Xx_NEWLINE_xXLocally-advanced or metastatic malignancy with an NTRK1, NTRK2 or NTRK3 gene fusion, identified through molecular assays as routinely performed at CLIA or other similarly-certified laboratories.Xx_NEWLINE_xXPatients must have histologic or cytological diagnosis of advanced/metastatic NSCLC with no curative treatment options; for those with mixed histology, there must be a predominant histologyXx_NEWLINE_xXHistologically confirmed triple negative breast cancer(TNBC) that is either locally recurrent, inoperable and cannot be treated with curative intent or is metastaticXx_NEWLINE_xXHave not received prior chemotherapy or targeted systemic therapy for their locally advanced inoperable or metastatic recurrence. Prior radiation therapy for recurrent disease is permittedXx_NEWLINE_xXParticipant must have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic.Xx_NEWLINE_xXHistologically and/or cytologically documented and radiographically measurable (by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) adenocarcinoma of the esophagus or stomach (HER2-positive or negative) that is metastatic/recurrent and not amenable to potentially curative treatment (e.g., inoperable metastatic or locally recurrent disease)Xx_NEWLINE_xXPatients with incurable, advanced or metastatic disease refractory to at least one previous line of therapyXx_NEWLINE_xXRegimen A only (monotherapy): Subjects with advanced metastatic solid tumorsXx_NEWLINE_xXRegimen B only (combination with trastuzumab): Subjects with advanced metastatic HER2+ solid tumorsXx_NEWLINE_xXRegimen C only (combination with cetuximab): Subjects with advanced metastatic EGFR+ solid tumorsXx_NEWLINE_xXBiopsy proven locally advanced or metastatic prostate cancer.Xx_NEWLINE_xXDocumented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic; patients with documented lymphomas.Xx_NEWLINE_xXLocally advanced or metastatic solid tumors that have exhausted standard of care therapyXx_NEWLINE_xXHistologically- or cytologically- confirmed locally advanced or metastatic nonfunctional well differentiated neuroendocrine tumor (WDNET)Xx_NEWLINE_xXPatients with locally advanced or metastatic RMC histologically confirmed by expert pathology review and loss of SMARCB1 staining by immunohistochemistry. Patients with advanced or metastatic unclassified renal cell carcinoma with medullary phenotype (a rare SMARCB1 negative RMC variant occurring in individuals without sickle hemoglobinopathies) are also eligible. The principal investigator (PI) is the final arbiter in questions related to eligibility.Xx_NEWLINE_xXHistological or cytological proof of pancreatic adenocarcinoma; must have locally advanced or metastatic pancreatic cancer and received at least one dose of chemotherapy (any treatment line) and may have responding, stable or progressive diseaseXx_NEWLINE_xXFemale patients with histologically-confirmed, unresectable locally advanced or metastatic breast cancer;Xx_NEWLINE_xXPatients should have had either progression during or after at least two HER2-targeting treatment regimens for locally advanced or metastatic disease or progression during or after (ado-)trastuzumab emtansine treatment for locally advanced or metastatic disease;Xx_NEWLINE_xXLocally advanced, unresectable disease, as defined by NCCN criteriaXx_NEWLINE_xXHas locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation.Xx_NEWLINE_xXAdvanced solid tumorsXx_NEWLINE_xXStage IV or locally advanced unresectable cancers for which no alternative therapies with proven survival advantage are availableXx_NEWLINE_xXPatients with recurrent unresectable locally advanced or metastatic urothelial carcinoma (also known as [aka] transitional cell carcinoma) previously NOT treated with systemic chemotherapy for current stage of disease\r\n* Low-dose chemotherapy (e.g., low-dose cisplatin, cisplatin plus fluorouracil (5-FU), mitomycin plus 5-FU, or cisplatin plus paclitaxel) given concurrently with radiation to the primary tumor site is not considered systemic chemotherapy; in that clinical setting, chemotherapy is given with the purpose of sensitizing the tumor to local radiation; it is not administered at doses with any systemic efficacy\r\n* Surgery is not considered first-line therapy following diagnosis of advanced/metastatic disease\r\n* If unresectable locally advanced urothelial cancer, could have been previously radiated, but must have Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 measurable, untreated progression of disease componentXx_NEWLINE_xXHas urothelial cancer that is suitable for local therapy administered with curative intent if not already administered; an example of local therapy with curative intent is treatment with chemotherapy and radiation for stage 3 disease; if unresectable locally advanced urothelial cancer, could have been previously radiated, but must have progression of disease component that is untreated and RECIST 1.1 measurableXx_NEWLINE_xXPatients must have histologically or cytologically confirmed, inoperable or unresectable locally advanced, or metastatic NSCLCXx_NEWLINE_xXHistologically or cytologically confirmed metastatic or unresectable locally advanced, non-squamous, NSCLCXx_NEWLINE_xXHistologically or cytologically confirmed diagnosis of metastatic or unresectable, locally advanced, recurrent NSCLC that has been previously treated (subjects who have failed adjuvant or locally advanced therapy within 6 months are also eligible to participate in the study)Xx_NEWLINE_xXPatients must have histologically confirmed breast cancer that is metastatic or locally advanced and unresectableXx_NEWLINE_xXStage IV disease or locally advanced/unresectable tumorsXx_NEWLINE_xXLocally advanced and unresectable or metastatic TNBC or triple negative inflammatory breast cancer.Xx_NEWLINE_xXParticipants must have locally advanced rectum cancer where primary resection without chemoradiotherapy (CRT) is unlikely to achieve clear margins as defined by magnetic resonance imaging (MRI), with no metastatic disease, as assessed by independent review.Xx_NEWLINE_xXSubjects must have histological or cytological documentation of locally advanced, recurrent, or metastatic renal cell carcinomaXx_NEWLINE_xXLocally advanced/unresectable disease as determined by site attending urologic oncologist or metastatic diseaseXx_NEWLINE_xXPatients must have histologically or cytologically confirmed invasive breast cancer, which is recurrent, locally advanced, unresectable or metastaticXx_NEWLINE_xXLocally advanced/non-operable or metastatic breast cancer that has not been previously treated in the metastatic setting with systemic therapy (i.e. first line treatment)Xx_NEWLINE_xXAdvanced or metastatic RCCXx_NEWLINE_xXNo more than three total prior systemic treatment regimens in the advanced or metastatic RCC settingXx_NEWLINE_xXHistologically or cytologically confirmed, previously treated, locally-advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) or other CA19-9 positive malignanciesXx_NEWLINE_xXPreviously treated, pathologically confirmed, locally advanced or metastatic solid tumors with measurable disease;Xx_NEWLINE_xXMust have histologically or cytologically documented rare tumor as defined per protocol that is metastatic or locally advanced and unresectable. Patients with locally advanced cutaneous squamous cell carcinoma that are technically resectable but in whom surgery is expected to lead to substantial function impairment or disfigurement are eligibleXx_NEWLINE_xXPatients must have either a histologically-confirmed metastatic or locally advanced prostate cancer, metastatic pancreatic cancer, melanoma or human papillomavirus (HPV) negative squamous cell carcinoma of head and neck.Xx_NEWLINE_xXPatient must have pathologically confirmed, locally advanced or metastatic pancreatic ductal adenocarcinoma (PDA) deemed surgically unresectable by a surgeon with expertise in pancreatic cancerXx_NEWLINE_xXEvidence of locally advanced or metastatic disease;Xx_NEWLINE_xXStage III unresectable locally advanced pancreatic carcinomaXx_NEWLINE_xXDiagnosed with advanced (metastatic or unresectable) leiomyosarcoma or liposarcomaXx_NEWLINE_xXPathologically confirmed adenocarcinoma of the pancreas; patients with either initially diagnosed or recurrent locally advanced disease; the maximum dimension of the treatment target must be =<10 cm; locally advanced disease defined as: T 1-2N+MO or T3-4 NxMo, or borderline resectable and unresectable adenocarcinoma without distant metastatic disease or resectable T3-4 NxMo disease or M1 with controlled distant diseaseXx_NEWLINE_xXSubjects must have a histologically confirmed metastatic and/or locally advanced sarcomaXx_NEWLINE_xXSubjects must have unresectable, recurrent, locally advanced, or metastatic neuroendocrine tumor including\r\n* Cohort A; unresectable, recurrent, locally advanced, or metastatic pheochromocytoma-paraganglioma (PC-PG) who have failed or are refractory to available therapies; sample size (N)=12\r\n* Cohort B will include only patients with unresectable, locally advanced or metastatic tumors who have failed or are refractory to available therapy; other neuroendocrine cancer varieties as characterized by expression of neuroendocrine markers on tumor tissue including CD56, synaptophysin, chromogranin and/or presence of a detectable serum or urine biomarker (3-methoxytyramine, normetanepherine, metanepherines, homovanillic acid [HVA], vanillylmandelic acid [VMA], and dopamine), varieties will include neuroblastoma, Ewing sarcoma, neuroectodermal tumor, clear call sarcoma, myoepithelial tumor, primitive neuroectodermal tumor [PNET], desmoplastic small round cell tumor, round cell sarcoma, and unresectable, metastatic or locally advanced , well-differentiated neuroendocrine tumors who have relapsed or are refractory to at least 2 systemic therapies (e.g. lanreotide, sunitinib, or everlimus); patients with small cell carcinomas will not be included in this clinical trial; N=12Xx_NEWLINE_xXPRE-SCREENING: Patients with advanced metastatic pancreatic cancer who have measurable diseaseXx_NEWLINE_xXPRE-SCREENING: Unresectable locally advanced or metastatic pancreatic cancer, confirmed by histology, and at least one but not more than two prior chemotherapy regimens with progression (neoadjuvant chemotherapy would not be counted as a line of therapy)Xx_NEWLINE_xXFULL STUDY INCLUSION CRITERIA: Unresectable locally advanced or metastatic pancreatic cancer and at least one but not more than two prior chemotherapy regimens with progression (neoadjuvant chemotherapy would not be counted as a line of therapy)Xx_NEWLINE_xXHistologically confirmed diagnosis of metastatic or advanced unresectable tumors that progressed on standard therapyXx_NEWLINE_xXInclusion Criteria:\n\n        Has histologically or cytologically confirmed, locally advanced, metastatic cancer meeting\n        the following criteria:\n\n        Phase 1 Expansion\n\n          1. Patient has failed all standard therapies or standard therapy does not exist or is not\n             tolerated.\n\n          2. Patient has specific FGF/FGFR aberrations\n\n               -  Intrahepatic or extrahepatic cholangiocarcinoma with FGFR2 gene fusions or other\n                  FGFR2 abnormalities, i.e., gene mutations (see Appendix A), rearrangements or\n                  amplifications\n\n               -  Glioblastoma or grade III glioma (i.e., anaplastic astrocytoma or anaplastic\n                  oligodendroglioma) with FGFR gene fusions or activating mutations.\n\n               -  Advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating mutations\n\n               -  All other tumor types harboring FGF9, FGF19 or FGFR2 amplifications (? 10\n                  copies), FGFR gene fusions, or FGFR activating mutations\n\n        Phase 2\n\n          1. Patient has histologically or cytologically confirmed, locally advanced, metastatic,\n             unresectable iCCA harboring FGFR2 gene fusions based on results from a NGS assay by\n             the Sponsor's designated central laboratory\n\n          2. Patient has been treated with and failed at least one prior systemic gemcitabine and\n             platinum-based chemotherapy for the advanced disease\n\n          3. Must have documentation of radiographic progression of disease on prior systemic\n             therapy\n\n          4. Patient has measurable disease as defined by Response Evaluation Criteria in Solid\n             Tumors (RECIST) guidelines (version 1.1, 2009) for advanced solid tumors or RANO\n             criteria (2010) for brain tumors.\n\n          5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1\n\n          6. Adequate organ function\n\n        Exclusion Criteria:\n\n        A patient will be excluded from this study if any of the following criteria are met:\n\n          1. History and/or current evidence of non-tumor related alteration of calcium-phosphorus\n             homeostasis.\n\n          2. History and/or current evidence of clinically significant ectopic\n             mineralization/calcification.\n\n          3. History and/or current evidence of clinically significant retinal disorder confirmed\n             by retinal examination.\n\n          4. A serious illness or medical condition(s)Xx_NEWLINE_xXLocally advanced disease that is not resectable or metastatic disease.Xx_NEWLINE_xXUnresectable advanced or metastatic RCC to include both clear cell and non-clear histologiesXx_NEWLINE_xXAdvanced Gastric CancerXx_NEWLINE_xXPatients with histologically or cytologically confirmed metastatic/advanced clear cell RCC, or RCC with a clear cell component, who have received 1 or 2 prior anti-angiogenic therapy regimens (+/- cytokine therapy with interleukin-2 or interferon-alfa) in the advanced or metastatic setting; examples of anti-angiogenic agents include, but are not limited to, sorafenib, sunitinib, pazopanib, axitinib, and bevacizumabXx_NEWLINE_xXPatients with stage IV metastatic cancer and/or cancer that is not amenable to surgery (i.e. must be curative intent; locally advanced is acceptable if completely resected)Xx_NEWLINE_xXLocally advanced unresectable or metastatic disease with no standard curative therapy availableXx_NEWLINE_xXPatients with histologically confirmed locally advanced or metastatic solid carcinomas in Arm 1Xx_NEWLINE_xXPatients with histologically confirmed locally advanced or metastatic colon cancer in Arm 2Xx_NEWLINE_xXPatients with histologically confirmed locally advanced or metastatic cholangiocarcinomas in Arm 3Xx_NEWLINE_xXPatients with histologically confirmed locally advanced or metastatic colon, gastric, ovarian, bladder cancers, as well as cholangiocarcinomas or hepatomas in Arm 4Xx_NEWLINE_xXAdvanced, unresectable hepatocellular carcinoma (unsuitable for resection, transplant or ablation)Xx_NEWLINE_xXPrior cetuximab permitted if it was given for no more than 9 doses in combination with radiation therapy or chemoradiation therapy for initial treatment of locally advanced or metastatic disease and completed at least 4 months prior to study enrollmentXx_NEWLINE_xXPatients must have advanced or metastatic NSCLCXx_NEWLINE_xXMale or female advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.Xx_NEWLINE_xXHistologically or cytologically confirmed metastatic or locally advanced adenocarcinoma of the pancreasXx_NEWLINE_xXNo more than one prior line of non-gemcitabine/nab-paclitaxel containing systemic therapy for metastatic/locally advanced pancreatic cancerXx_NEWLINE_xXMore than one systemic therapy regimen of any type for metastatic or locally advanced disease; adjuvant gemcitabine that ended more than 6 months prior to diagnosis of recurrent disease is not considered as a regimenXx_NEWLINE_xXPatients must have pathologically confirmed advanced/metastatic cancer prior to enrollment.Xx_NEWLINE_xXHistologic proof of metastatic or locally advanced, unresectable breast cancerXx_NEWLINE_xXMetastatic and/or locally advanced or locally recurrent disease that is not surgically resectableXx_NEWLINE_xXPatients must have advanced disease that is not amenable to transplant or resectionXx_NEWLINE_xXHistologically or cytological confirmed diagnosis of metastatic or locally advanced, unresectable pancreatic adenocarcinoma (excluding other pancreatic malignancies for example, acinar cell carcinomas, adenosquamous carcinomas, and neuroendocrine islet cell neoplasms).Xx_NEWLINE_xXPatients with borderline resectable, locally advanced or metastatic diseaseXx_NEWLINE_xXStage IV or locally advanced histologically confirmed solid tumors for which no alternative therapies with proven survival advantage are availableXx_NEWLINE_xXHistologically or cytologically documented locally advanced, inoperable or metastatic solid tumors with documented AKT1, 2, 3 genetic alterations, activating PI3K mutations, PTEN-null, or other known actionable PTEN mutationsXx_NEWLINE_xXHistologically or cytologically confirmed adenocarcinoma of the breast with evidence of metastatic disease (stage IV) or locally advanced disease, not amenable to surgery or radiation with curative intentXx_NEWLINE_xXPancreatic Cancer Cohort: Patients must have a diagnosis of locally advanced or metastatic pancreatic adenocarcinoma previously treated with or not a candidate for standard of care systemic therapy.Xx_NEWLINE_xXHistologically confirmed, locally-advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) or other CA19-9 positive malignanciesXx_NEWLINE_xXPatients must have histologically or cytologically documented carcinoma primary to the intra- or extra-hepatic biliary system or gall bladder with clinical and/or radiologic evidence of unresectable, locally advanced or metastatic disease; patients with ampullary carcinoma are not eligibleXx_NEWLINE_xXHistologically documented non-keratinizing locally advanced recurrent or metastatic NPC.Xx_NEWLINE_xXPrior chemotherapy for advanced or metastatic diseaseXx_NEWLINE_xXHistologic or cytological diagnosis of SQCLC with advanced/metastatic stage, with no known curative treatment options; prior platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation therapy given for locally advanced disease is considered first line therapy only if recurrent (local or metastatic) disease developed within 6 months of completing therapy; subjects with recurrent disease > 6 months will be eligibleXx_NEWLINE_xXTo be eligible for Cohorts 1-4, patients must have failed one or two prior lines of systemic therapy for advanced/metastatic diseaseXx_NEWLINE_xXTo be eligible for Cohort 6, patients must have failed one prior line of systemic therapy for advanced/metastatic diseaseXx_NEWLINE_xXTo be eligible for Cohort 5, patients must not have received any systemic therapy for advanced/metastatic diseaseXx_NEWLINE_xXHistologically or cytologically proven diagnosis of breast cancer with evidence of metastatic or locally advanced disease, not amenable to resection or radiation therapy with curative intentXx_NEWLINE_xXMetastatic or unresectable locally advancedXx_NEWLINE_xXFor Part I (Arms A, B): Patients can have either locally advanced or metastatic pancreas adenocarcinoma for which no prior therapy has been administered for either locally advanced or metastatic disease; prior adjuvant therapy is permissible if gemcitabine or a fluoropyrimidine was administered with or without radiation and if disease recurrence has been documented at least 6 months after completion of adjuvant therapyXx_NEWLINE_xXPatients with histologically or cytologically-confirmed, locally advanced, or metastatic solid malignancy that is relapsed, refractory, or progressing following at least 1 prior systemic therapy (Part A)Xx_NEWLINE_xXPatients in Part B must have histologically or cytologically-confirmed, locally-advanced, or metastatic solid malignancy within the disease indications of Part AXx_NEWLINE_xXPhase 1: Subjects must have previously received and progressed on or after treatment with an EGFR tyrosine kinase inhibitor (TKI). Additional lines of systemic therapy including investigational agents for locally advanced or metastatic NSCLC are allowed.Xx_NEWLINE_xXPrior systemic therapy directed at advanced or metastatic RCCXx_NEWLINE_xXMuscle-invasive, locally advanced nonresectable, or metastatic urothelial carcinoma (i.e., T2, T3, T4, and / or stage IV)Xx_NEWLINE_xXThat is relapsed or refractory after treatment with an approved therapy(ies), defined as metastatic or non-resectable, locally advanced disease that has previously been treated with and progressed following approved therapy(ies) (Cohort 2)Xx_NEWLINE_xXReceived >2 prior systemic anti-cancer drug regimen for locally advanced diseaseXx_NEWLINE_xXNon-hepatocellular carcinoma subjects must have received at least 1 prior standard of care systemic anti-cancer therapy for their locally advanced or metastatic disease.Xx_NEWLINE_xXARM A COHORT 1: Patients must have advanced pancreatic adenocarcinoma (unresectable or metastatic)Xx_NEWLINE_xXHistologically or cytologically confirmed locally advanced, inoperable, or metastatic tumors: • Carboplatin Plus Paclitaxel Arm:Xx_NEWLINE_xXSubjects who were previously treated with carboplatin and paclitaxel for locally advanced and/or metastatic disease and who received the last dose of the drug(s) ? 12 months prior to the first dose of the study treatment may be enrolledXx_NEWLINE_xXSubjects who were not previously treated with carboplatin and paclitaxel for locally advanced and/or metastatic disease and for whom, in the opinion of the Investigator, this chemotherapy regimen is appropriate may be enrolledXx_NEWLINE_xXSubjects who were previously treated with paclitaxel for locally advanced and/or metastatic disease and who in the opinion of the Investigator may benefit from the combination treatment of ARQ 092 and paclitaxel may be enrolledXx_NEWLINE_xXSubjects who were not previously treated with paclitaxel for locally advanced and/or metastatic disease and for whom, in the opinion of the Investigator, this chemotherapy regimen is appropriate may be enrolledXx_NEWLINE_xXHave locally advanced or metastatic urothelial cancer that is not amenable to curative surgical treatment\r\n* Have histologically or cytologically confirmed urothelial tract carcinomaXx_NEWLINE_xXPatients must have histologic or cytologic diagnosis of advanced/metastatic NSCLC. For those with mixed histology, there must be a predominant histology.Xx_NEWLINE_xXCytologic or histologic proof of adenocarcinoma of the pancreas; patients can have tumor which is locally advanced or borderline resectable; unequivocal metastases and islet cell tumors are not eligibleXx_NEWLINE_xXMetastatic or locally advanced breast cancer for which endocrine therapy is an appropriate treatment optionXx_NEWLINE_xXPatients must have histologically or cytologically confirmed advanced, incurable cancers of the esophagus, liver, stomach, small bowel, pancreas, bile duct, colon or rectum and be eligible to receive chest, abdominal and/or pelvic radiation therapy (RT) for palliation; documentation of this is required in physician note; concomitant systemic therapy is not allowed during administration of palliative RT; palliative RT can be considered for advanced primary tumors or metastatic disease as aboveXx_NEWLINE_xXAdvanced disease (Masaoka staging) not amenable to curative treatmentXx_NEWLINE_xXPatients eligible for this study should have locally and/or regionally advanced melanoma that is considered potentially surgically resectable and with biopsiable tumor at baselineXx_NEWLINE_xXPatients with histologically documented locally advanced, recurrent and/or metastatic NSCLCXx_NEWLINE_xXFor dose escalation cohort: patients with histologically or cytologically confirmed locally advanced or metastatic solid tumors who have failed at least one line of therapyXx_NEWLINE_xXLocally advanced or metastatic pancreatic cancer for the pancreatic cancer cohortXx_NEWLINE_xXLocally advanced or metastatic disease not amenable to surgeryXx_NEWLINE_xXPreviously treated for advanced cancer and there are no curative therapy options availableXx_NEWLINE_xXArm 2: histologically or cytologically confirmed adenocarcinoma of the pancreas that is locally advanced or metastaticXx_NEWLINE_xXArms 2, 2E, 3, 3E: patients who previously received > 2 lines of systemic chemotherapy for advanced or metastatic diseaseXx_NEWLINE_xXLocally advanced or metastatic CRCXx_NEWLINE_xXRENAL CELL CARCINOMA (RCC) COHORT INCLUSION CRITERIA: History of histologically-proven locally advanced or metastatic (cT2a-T4NanyMany) chromophobe RCCXx_NEWLINE_xXPathologically confirmed advanced pancreatic cancer defined as non-operable in a curative intent, locally recurrent, or metastatic diseaseXx_NEWLINE_xXPatients must have histologically-proven locally-recurrent or metastatic solid tumor; the first 10 patients may have cancer of any histology; preference will be given to patients with metastatic ovarian cancer, breast cancer, and malignant melanoma, as these malignancies have been shown to be sensitive to manipulation of the beta-adrenergic receptor; the final twenty-five patients to be accrued must have locally-recurrent or metastatic malignant melanoma that is not surgically resectableXx_NEWLINE_xXDisease progression after prior therapy in locally advanced or metastatic settingXx_NEWLINE_xXIn the phase Ib portion, must have locally advanced or metastatic GIST and have progressed on imatinibXx_NEWLINE_xXPatients with advanced malignant hepatic tumors.Xx_NEWLINE_xXStage IV or locally advanced cancers for which no alternative therapies with proven survival advantage are availableXx_NEWLINE_xXHistologically or cytologically documented, incurable, unresectable locally advanced, or metastatic breast cancerXx_NEWLINE_xXHave an unresectable, locally advanced pancreatic cancer (AJCC stage III). (Excluded: resectable and borderline resectable patients are ineligible per NCCN criteria)Xx_NEWLINE_xXLocally advanced or metastatic breast cancerXx_NEWLINE_xXPhase II: Patients must have histologically or cytologically confirmed locally advanced, unresectable or metastatic carcinoma of the breastXx_NEWLINE_xXPresence of locally advanced, inoperable or metastatic diseaseXx_NEWLINE_xXPreviously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.Xx_NEWLINE_xXPreviously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.Xx_NEWLINE_xXPreviously treated with one or more regimen of systemic therapy for locally advanced or metastatic disease.Xx_NEWLINE_xXPreviously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.Xx_NEWLINE_xX(Combination Therapy - Part E and Part F) -- Histologically or cytologically confirmed advanced or metastatic solid malignancy for which pembrolizumab treatment is approved. In Part F, other advanced solid tumor indications may be eligible as identified by the Sponsor.Xx_NEWLINE_xXFor the dose escalation phase, patients must have histologically confirmed metastatic solid tumor (metastatic or unresectable, locally advanced gastrointestinal [GI] cancers [e.g., esophageal, colorectal, pancreatic and others]), ovarian and breast cancers; the malignancy should be considered incurable using standard treatment; for the extension cohort (N=12) and for the expansion phase (N=45), patients with advanced breast cancer (N=15), advanced gastrointestinal cancer (N=15) and advanced ovarian (N=15) will be enrolled; all patients enrolled on the extension and expansion phase will be required to have measurable diseaseXx_NEWLINE_xXPatients with histologically proven small cell carcinoma of the bladder, or elsewhere along the urothelium, which is locally advanced or metastatic (i.e. > or = cT3b, > or = pT3b, N+, or M+) at the time of presentation or cystectomy who have been treated with chemotherapyXx_NEWLINE_xXAdvanced myelofibrosisXx_NEWLINE_xXHistologically or cytologically confirmed diagnosis of metastatic or locally advanced unresectable tumorsXx_NEWLINE_xXSubject has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to the first dose of study treatment.Xx_NEWLINE_xXDocumented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic; patients with documented lymphomas.Xx_NEWLINE_xXHistological or cytological documentation of squamous cell carcinoma of the head and neck (SCCHN) (oral cavity, oropharynx, hypopharynx, or larynx) that is recurrent, locally advanced, or metastatic and is not amenable to curative treatment options, surgery or definitive chemoradiation therapy.Xx_NEWLINE_xXPatients with histologically confirmed, locally advanced, unresectable, or metastatic solid tumors or hematological malignancies that progressed while on or after PD-1/PD-L1 containing therapy;Xx_NEWLINE_xXTumor progression during or after first-line treatment for advanced unresectable / metastatic ESCCXx_NEWLINE_xXReceipt of 2 or more prior systemic treatments for advanced/metastatic unresectable ESCCXx_NEWLINE_xXadvanced or metastatic solid tumor (Part A)Xx_NEWLINE_xXLocally advanced (T4b, any N; or any T, N 2?3) or metastatic disease (any T, any N and M1). Locally advanced bladder cancer must be unresectable i.e. invading the pelvic or abdominal wall (stage T4b) or presenting with bulky nodal disease (N2-3).Xx_NEWLINE_xXWomen with histologically or cytologically confirmed breast cancer with evidence of metastatic or locally advanced disease not amenable to any local therapy with curative intent.Xx_NEWLINE_xXPatients with histological confirmation of locally advanced or metastatic NSCLCXx_NEWLINE_xXLocally advanced lung cancer candidate for curative treatment through radical surgery and/or radio(chemo)therapyXx_NEWLINE_xXPrior or concomitant systemic anti-cancer treatment for advanced diseaseXx_NEWLINE_xXHas a pathologically documented advanced/unresectable or metastatic breast cancerXx_NEWLINE_xXPart 1: Has a histologically- or cytologically-documented, locally-advanced or metastatic solid malignancy and has received ?1 and <6 prior line of cancer treatment regimen(s).Xx_NEWLINE_xXLocally recurrent/metastatic.Xx_NEWLINE_xXAll parts except Part B, Part E2, and Part E3 dose expansion: Must have diagnosis of cancer that is advanced or metastaticXx_NEWLINE_xXPart E2 dose expansion: must have cancer that is advanced or metastatic and have prior documentation of a mutation of PIK3CAXx_NEWLINE_xXAdvanced (clinical stage T4b, unresectable) or metastatic diseaseXx_NEWLINE_xXHistologically proven, metastatic or locally advanced non resectable, or recurrent post surgery GISTXx_NEWLINE_xXConfirmed locally advanced or metastatic non-small cell lung cancer that is unresectableXx_NEWLINE_xXHistologically or cytologically proven metastatic or locally advanced disease. Specifically:Xx_NEWLINE_xXSubjects who have received up to 3 lines of therapy for advanced disease, without prior exposure to taxane in the advanced stage settingXx_NEWLINE_xXHistological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors that are not amenable for treatment with curative intentXx_NEWLINE_xXPatients with histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumor disease for which standard therapy is not effective, available, acceptable, or is intolerable.Xx_NEWLINE_xXHave advanced (not amenable to potentially curative surgery) or metastatic RCCXx_NEWLINE_xXRetroperitoneal/hilar adenopathy concerning for locally advanced diseaseXx_NEWLINE_xXPhase I only: Diagnosis of advanced/metastatic NSCLC for which no standard treatment option; Phase II only: Advanced NSCLC patients who have received at least 1 platinum-based systemic chemotherapy regimenXx_NEWLINE_xXHistologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma with locally advanced or metastatic diseaseXx_NEWLINE_xXAdvanced metastatic, progressing carcinoid or pancreatic islet cell cancersXx_NEWLINE_xXLocally advanced/unresectable (as determined by local surgeon) OR metastatic diseaseXx_NEWLINE_xXLocally advanced (T4b, any N; any T, N2-3) or metastatic (M1) disease as determined by the treating investigatorXx_NEWLINE_xXMetastatic disease or locally-advanced disease not amenable to curative intent treatmentXx_NEWLINE_xXGroup 2 - patients must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET rearrangement that was not previously treated with a TKI that inhibits RET.Xx_NEWLINE_xXPathologically confirmed, advanced (unresectable or metastatic):Xx_NEWLINE_xXHave locally advanced (unresectable) or metastatic small bowel adenocarcinomaXx_NEWLINE_xXUnresectable locally advanced or metastatic histologically proven HER2+ gastroesophageal junction (GEJ) or gastric adenocarcinoma.Xx_NEWLINE_xXPhase 2 only: Infants from birth and older at C1D1 with a locally advanced or metastatic infantile fibrosarcoma, patients with locally advanced infantile fibrosarcoma who would require, in the opinion of the Investigator, disfiguring surgery or limb amputation to achieve a complete surgical resection or birth through 21 years of age at C1D1 with a locally advanced or metastatic solid tumor or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies and for which no standard or available systemic curative therapy exists with a documented NTRK gene fusion (or in the case of infantile fibrosarcoma, congenital medoblastic nephroma or secretory breast cancer with documented ETV6 rearrangement by FISH or RT-PCR or a documented NTRK fusion by NGS) (identified through molecular assays as routinely performed at CLIA or other similarly-certified laboratories) or (including Expansion Phase) potential patients older than 21 years of age with a tumor diagnosis with histology typical of a pediatric patient and an NTRK fusion may be considered for enrollment following discussion between the local site Investigator and the Sponsor's Medical Monitor. Patients with NTRK-fusion positive benign tumors are also eligible.Xx_NEWLINE_xXPatients must have histologically confirmed locally advanced or metastatic pancreas cancerXx_NEWLINE_xXHistological or cytological proof of pancreatic adenocarcinoma; must have locally advanced or metastatic pancreatic cancer who have received at least first line chemotherapy and may have responding, stable or progressive diseaseXx_NEWLINE_xXPatients must have histologically or cytologically confirmed advanced leiomyosarcoma of the uterus (ULMS); advanced ULMS is defined as metastatic ULMS or unresectable primary ULMSXx_NEWLINE_xXHave metastatic melanoma or NSCLC, or locally advanced NSCLC not suitable for curative-intent local therapyXx_NEWLINE_xXPSTAT3 SCREENING: Participants must have histologically or cytologically confirmed invasive breast cancer (testing of either the primary tumor or in the metastatic setting), with either metastatic disease or unresectable locally advanced disease (including inflammatory breast cancer); patients without pathologic or cytologic confirmation of metastatic disease (or unresectable locally advanced disease) should have unequivocal evidence of metastasis (or unresectable locally advanced disease) by physical examination or radiologic studyXx_NEWLINE_xXParticipants must have histologically or cytologically confirmed invasive breast cancer with either metastatic disease or unresectable locally advanced disease; patients without pathologic or cytologic confirmation of metastatic disease (or unresectable locally advanced disease) should have unequivocal evidence of metastasis (or unresectable locally advanced disease) by physical examination or radiologic studyXx_NEWLINE_xX-  Histologically or cytologically confirmed metastatic or unresectable locally advanced\n             NSCLCXx_NEWLINE_xXNo evidence of locally advanced or metastatic diseaseXx_NEWLINE_xXPatients must have histologically confirmed localized or locally advanced breast cancer for which the treatment plan includes chemotherapy with 4 cycles of standard TC (docetaxel 75 mg/m^2 and cyclophosphamide 600mg/m^2)Xx_NEWLINE_xXMust have locally advanced or distant metastatic disease that is not surgically curableXx_NEWLINE_xXPatients with locally advanced bladder cancer based on cross-sectional imaging (suspicion of extravesical disease or hydronephrosis)Xx_NEWLINE_xXAdult with unresectable locally advanced or metastatic renal cell carcinoma with a clear cell componentXx_NEWLINE_xXLocally advanced or metastatic malignancyXx_NEWLINE_xXTNBC must be either locally recurrent or metastatic; locally recurrent disease must not be amenable to surgical resection or radiation with curative intentXx_NEWLINE_xXBiopsy proven locally advanced breast cancer: IIB, IIIA and IIIBXx_NEWLINE_xXPatients must have histologically or cytologically confirmed metastatic or unresectable locally advanced adenocarcinoma of the pancreas with no prior systemic therapy for metastatic or locally advanced diseaseXx_NEWLINE_xXPHASE II: Patients must NOT have locally advanced diseaseXx_NEWLINE_xXPatients with advanced malignant solid tumors are excludedXx_NEWLINE_xXLocally advanced or metastatic breast cancerXx_NEWLINE_xXHistologically proven adenocarcinoma of the breast in the primary or metastatic setting; stage: locally advanced (inoperable) or metastaticXx_NEWLINE_xXAdvanced or metastatic RCCXx_NEWLINE_xXDose Expansion: Histologically confirmed and documented, previously untreated or treated stage IIIB or IV Non-Small Cell Lung Cancer (NSCLC) having failed no more than 1 previous platinum containing chemotherapy regimen for locally advanced or metastatic disease or relapsed/refractory locally advanced or metastatic gastric adenocarcinoma having failed no more than 2 previous chemotherapy regimen for locally advanced or metastatic disease. Subjects with NSCLC who are known to be epidermal growth factor receptor (EGFR)-mutation positive must have received an EGFR inhibitor and subjects known to be anaplastic lymphoma kinase (ALK)-mutation positive must have received an ALK inhibitor. Prior to enrollment, confirmation of the following must be obtained: • Dose expansion - For subjects in the dose expansion portion of the study, it is mandatory that available archived tumor tissue in FFPE block or minimum 10 unstained consecutive core biopsy slides from 1 archival block that meet specific tissue requirements are available.Xx_NEWLINE_xXMetastatic or locally advanced diseaseXx_NEWLINE_xXNo more than 5 prior anticancer regimens for advanced (recurrent, locally advanced or metastatic) disease except for patients with GBM which must have first recurrence of GBM by diagnostic biopsy or contrast enhanced magnetic resonance imaging (MRI).Xx_NEWLINE_xXHas histologically- or cytologically-confirmed diagnosis of locally advanced unresectable or metastatic gastric or GEJ adenocarcinomaXx_NEWLINE_xXHistologic confirmation of advanced solid tumorsXx_NEWLINE_xXFor Phase 1: Subjects who have advanced or metastatic disease as noted above that have received at least one prior therapy or have advanced or metastatic disease for which no curative treatment is available may be enrolled.Xx_NEWLINE_xXSubject must have received at least 1 prior systemic regimen for advanced or metastatic diseaseXx_NEWLINE_xXSubjects with histological confirmation of locally advanced unresectable or metastatic MSI high CRC.Xx_NEWLINE_xXHistologically or cytologically confirmed breast cancer that is either locally advanced or metastatic. Locally advanced breast cancer must not be amenable to surgical resection or radiation with curative intent.Xx_NEWLINE_xXLocally advanced breast cancer that is not amenable to curative radiation or surgical cure and/or metastatic disease appropriate for systemic single cytotoxic chemotherapyXx_NEWLINE_xXNo more than 3 prior chemotherapy-inclusive regimens for locally advanced and/or metastatic disease (no limit on prior hormonal therapies or targeted anticancer therapies such as mechanistic target of rapamycin (mTOR) or CDK4/6 inhibitors, immune-oncology agents, tyrosine kinase inhibitors, or monoclonal antibodies against CTL4 or VEGF)Xx_NEWLINE_xXHas received no prior systemic chemotherapy for advanced or metastatic urothelial carcinoma, with the following exceptions:Xx_NEWLINE_xXunresectable locally advanced recurrent BC or metastatic BCXx_NEWLINE_xXat least 2 HER2-directed therapies for advanced diseaseXx_NEWLINE_xXPatient has histologically proven advanced (unresectable) or metastatic cancer as outlined below according to study phase and disease type:Xx_NEWLINE_xXSubjects with histologically confirmed unresectable locally advanced or metastatic adenocarcinoma of the stomach or gastro-esophageal junction (GEJ)Xx_NEWLINE_xXPrior chemotherapy for unresectable locally advanced or metastatic adenocarcinoma of the stomach or gastro-esophageal junction (GEJ)Xx_NEWLINE_xXHistologically or cytologically documented, locally advanced or metastatic NSCLC.Xx_NEWLINE_xXSubjects with histologically confirmed locally advanced or metastatic disease of the following tumor types:Xx_NEWLINE_xXReceipt of more than 2 prior systemic therapies for advanced HCC.Xx_NEWLINE_xXInclusion Criteria:\n\n        General Inclusion Criteria:\n\n          -  Histologically or cytologically documented advanced solid tumors\n\n          -  Adequate hematologic and end organ function\n\n          -  Measurable disease by RECIST v1.1\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1\n\n          -  Resolution of any acute, clinically significant treatment-related toxicity from prior\n             therapy to Grade less than or equal to (</=) 1 prior to study entry, with the\n             exception of alopecia\n\n        Eligible Tumor Types:\n\n        Arm A Escalation Cohorts and Arms A and B Biopsy Cohort (Cutaneous/Subcutaneous Lesions)\n\n          -  Histologically or cytologically documented, incurable or metastatic solid malignancy\n             that has failed all available or acceptable standard therapy for which the participant\n             is eligible Arm A and B Safety Expansion Cohorts, Arm B Escalation Cohorts, and Arm B\n             Biopsy Cohort (Liver Lesions)\n\n          -  Histologically or cytologically confirmed metastatic colorectal cancer (mCRC).\n             Participants in the Arm A Safety Expansion Cohort must have mCRC for which established\n             therapies have proved ineffective or intolerable. Participants with malignancies other\n             than mCRC within 5 years prior to Day 1 (except for those with a negligible risk of\n             metastasis or death, such as adequately treated carcinoma in situ of the cervix, basal\n             or squamous cell skin cancer, localized prostate cancer treated surgically with\n             curative intent, or ductal carcinoma in situ treated surgically with curative intent)\n             are not eligible.\n\n        Arm A renal cell carcinoma (RCC) Cohort:\n\n        - Histologically or cytologically confirmed advanced or metastatic RCC with a clear cell\n        component.\n\n        Arm A Tumor Type-Specific Cohort:\n\n        Gastric Cancer:\n\n        - Histologically or cytologically confirmed locally advanced or metastatic adenocarcinoma\n        of the stomach or gastroesophageal junction for which established therapies have proved\n        ineffective or intolerable. The decision may be made to restrict enrollment to participants\n        with a specified tumor PD-L1 status (e.g., immunohistochemistry [IHC] status 0/1 or 2/3)\n\n        Ovarian Cancer:\n\n        - Measurable/assessable ovarian cancer (defined as epithelial ovarian, fallopian tube, or\n        primary peritoneal cancer) that has progressed less than (<) 6 months after completing\n        platinum-based therapy. The following histological types are eligible: Adenocarcinoma NOS,\n        clear cell adenocarcinoma, endometriod adenocarcinoma, malignant Brenner's tumour, mixed\n        epithelial carcinoma, mucinous adenocarcinoma, serous adenocarcinoma, transitional cell\n        carcinoma, undifferentiated carcinoma\n\n        Bladder Cancer:\n\n          -  Histologically or cytologically documented locally advanced (T4b, any N; or any T, N\n             2-3) or metastatic (M1, Stage IV) transitional cell carcinoma of the urothelium\n             (including renal pelvis, ureters, urinary bladder, urethra)\n\n          -  Participants with mixed histologies are required to have a dominant transitional cell\n             pattern\n\n          -  Locally advanced bladder cancer must be inoperable based on involvement of pelvic\n             sidewall or adjacent viscera (clinical stage T4b) or bulky nodal metastasis (N2-N3)\n\n          -  Disease progression during or following treatment with at least one\n             platinum-containing regimen (e.g., GC, MVAC, CarboGem, etc.) for inoperable locally\n             advanced or metastatic urothelial carcinoma or disease recurrence\n\n        Cervical Cancer:\n\n          -  Persistent or recurrent squamous cell carcinoma of the cervix (including adenosquamous\n             tumors)\n\n        Arms C, D, and E Cohorts:\n\n        - Histologically or cytologically documented Stage IIIB (not eligible for definitive\n        chemoradiotherapy), Stage IV, or recurrent non-small cell lung cancer (NSCLC)\n\n        Arm F Cohort:\n\n          -  Histologically confirmed estrogen receptor (ER)-, progesterone receptor (PR)-, and\n             human epidermal growth factor receptor (HER)-negative (triple-negative) adenocarcinoma\n             of the breast that has been treated with systemic cytotoxic therapy. Locally recurrent\n             disease must not be amenable to resection with curative intent\n\n          -  Participants with tumors amenable to excisional, punch, or core needle biopsy are\n             eligible for a separate biopsy expansion cohort\n\n        Tumor molecular status:\n\n        Arm A safety expansion cohort\n\n        - Up to 10 participants with CRC and high microsatellite instability (MSI-H) may be\n        enrolled\n\n        Exclusion Criteria:\n\n        General Exclusions\n\n          -  Any approved anti-cancer therapy, including chemotherapy, hormonal therapy,\n             radiotherapy, or herbal therapy intended as anti-cancer therapy, within 3 weeks prior\n             to initiation of study treatment; the following are allowed: hormonal therapy with\n             gonadotropin-releasing hormone agonists or antagonists for prostate cancer,\n             hormone-replacement therapy, and palliative radiotherapy for bone metastases greater\n             than (>) 2 weeks prior to Day 1\n\n          -  Bisphosphonate therapy for symptomatic hypercalcemia\n\n          -  Known clinically significant liver disease\n\n          -  Known primary central nervous (CNS) malignancy or active CNS metastases (progressing\n             or requiring anticonvulsants or corticosteroids for symptomatic control)\n\n          -  Pregnant or lactating women\n\n          -  Known hypersensitivity to Chinese hamster ovary cell products or any component of the\n             atezolizumab formulation\n\n          -  History of autoimmune disease, idiopathic pulmonary fibrosis, human immunodeficiency\n             virus (HIV), hepatitis B or C infection; history of hepatitis B is allowed if\n             infection has resolved (absence of hepatitis B surface antigen [HBsAg])\n\n          -  Severe infections within 4 weeks prior to Day 1, or signs or symptoms of significant\n             infection within 2 weeks prior to Day 1\n\n          -  Received oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1\n\n          -  History of myocardial infarction, unstable angina stroke or transient ischemic attack\n             within 6 months prior to Day 1\n\n          -  Administration of a live, attenuated vaccine within 4 weeks before Day 1 or\n             anticipation that such a live attenuated vaccine will be required during the study\n             Bevacizumab-Specific Exclusions (Arms A and B) Exclusion Criteria Unique to Arm A RCC\n             Cohort\n\n          -  Any prior systemic treatment (including tyrosine kinase inhibitors, antibody therapy,\n             immunotherapy, chemotherapy, hormonal therapy, or investigational therapy) for RCC.\n             All treatments, neo-adjuvant, adjuvant, or for locally advanced or metastatic RCC are\n             not permitted\n\n        Arm A Tumor Type-Specific Cohort:\n\n        Gastric Cancer:\n\n        - Prior approved or experimental anti-vascular endothelial growth factor or its receptor\n        (VEGF/VEGFR) therapy (including, for example, bevacizumab or nintedanib). The decision may\n        be made to allocate a specified number of slots to participants who have received prior\n        anti-VEGF/VEGFR therapy\n\n        Ovarian Cancer:\n\n          -  Refractory disease\n\n          -  History of bowel obstruction\n\n          -  >2 prior anticancer regimens\n\n          -  Prior approved or experimental anti-VEGF/VEGFR therapy (including, for example,\n             bevacizumab or nintedanib)\n\n        Cervical Cancer:\n\n        - > 2 prior cytotoxic regimens, not including prior cisplatin-based chemotherapy\n        concomitantly administered with primary pelvic radiation\n\n        Exclusion Criteria Unique to Arm B:\n\n          -  Prior treatment with an oxaliplatin-containing regimen. Oxaliplatin >12 months prior\n             to the diagnosis of metastatic disease is permitted.\n\n          -  Known dihydropyrimidine dehydrogenase deficiency or thymidylate synthase gene\n             polymorphism predisposing the participant for 5-FU toxicity\n\n        Exclusion Criteria Unique to Arms C, D, and E:\n\n          -  Prior chemotherapy for locally advanced or metastatic NSCLC\n\n          -  For participants who received prior adjuvant/neo-adjuvant chemotherapy or\n             chemoradiation for NSCLC, a treatment-free interval >6 months between the last\n             treatment administration and the date of recurrence in required\n\n          -  Participants with a known epidermal growth factor receptor (EGFR) sensitizing mutation\n             must have experienced disease progression during or after treatment with an approved\n             EGFR tyrosine kinase inhibitor\n\n          -  Participants with a known anaplastic lymphoma kinase (ALK) fusion oncogene must have\n             experienced disease progression during or after treatment with crizotinib\n\n          -  For Arm D (carboplatin + pemetrexed), squamous cell histology or evidence of mixed\n             NSCLC histology with a predominance of the squamous cell type\n\n          -  For Arm D (carboplatin + pemetrexed), inability to discontinue treatment with\n             non-steroidal anti-inflammatory drugs (NSAIDs) for 5 days\n\n        Exclusion Criteria Unique to Arm F:\n\n          -  Prior therapy with more than two cytotoxic regimens for metastatic or locally advanced\n             triple-negative breast cancer (TNBC)\n\n          -  Treatment with a taxane-containing regimen within 6 months before enrollmentXx_NEWLINE_xXHave histologically or cytologically confirmed, locally advanced or unresectable or metastatic urothelial (transitional cell) carcinoma of the bladder, urethra, ureter, or renal pelvis.Xx_NEWLINE_xXLocally advanced, relapsed, and/or metastatic cancerXx_NEWLINE_xXFor dose escalation, locally advanced and/or metastatic gastrointestinal (GI) solid tumor in participants who have progressed on a standard therapy, are intolerant to SOC, and/or are non-amenable to SOC and other solid tumors expressing CEA. Only locally advanced and/or metastatic colorectal cancer participants should be included in the scheduled comparison expansionXx_NEWLINE_xXSubject has a confirmed diagnosis of advanced unresectable solid tumors in the target subject population within the parameters mentioned:Xx_NEWLINE_xXSubject has a definitive histologically or cytologically confirmed locally advanced or metastatic adenocarcinoma of the pancreas. Subjects with islet cell neoplasms are excluded.Xx_NEWLINE_xXnab-Paclitaxel and Nivolumab: Subjects must have received 1 prior systemic chemotherapy regimen for locally advanced or metastatic disease.Xx_NEWLINE_xXPhase I (Cohorts A through D, G, H, T, T2 and X): Histologically documented, locally advanced or metastatic solid malignancy or NHL that has progressed or failed to respond to at least one prior regimen and are not candidates for regimens known to provide clinical benefitXx_NEWLINE_xXPhase I (Cohorts E and F): Post-menopausal females with locally advanced or metastatic hormone receptor-positive breast cancer that has progressed or failed to respond to at least one prior endocrine therapy in the adjuvant or metastatic settingXx_NEWLINE_xXParticipants must have histologically or cytologically confirmed invasive breast cancer, with unresectable locally advanced or metastatic disease; participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluationXx_NEWLINE_xXMetastatic or locally-advanced, histologically documented TNBC (absence of HER2, ER, and PR expression)Xx_NEWLINE_xXLocally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.Xx_NEWLINE_xXPhase 1: Subjects with advanced or metastatic solid tumors.Xx_NEWLINE_xXHistologically confirmed locally advanced (e.g. unresectable) or metastatic angiosarcoma that has progressed by RECIST following treatment with prior systemic treatment. . Prior pazopanib is allowed if the drug was not discontinued for toxicity (Phase 2 angiosarcoma cohort).Xx_NEWLINE_xXSubject must have locally advanced or metastatic solid tumor;Xx_NEWLINE_xXSubjects with any previously treated advanced (metastatic or refractory) solid tumorXx_NEWLINE_xXHas not received prior systemic treatment for their advanced/metastatic NSCLC.Xx_NEWLINE_xXPhase 2 only: Previous treatment with >3 chemotherapy regimens for locally advanced or metastatic diseaseXx_NEWLINE_xXAdult women (? 18 years of age) with metastatic or recurrent locally advanced BC, not amenable to curative treatment by surgery or radiotherapy, with objective evidence of disease progression.Xx_NEWLINE_xXLocally advanced, relapsed, and/or metastatic cancer with low or minimal tumor burden which may or may not be measurable; no tumor size criteria are used.Xx_NEWLINE_xXVLA009A: Locally advanced and/or metastatic disease for which curative surgery and/or radiation therapy is not possible and judged not to be a candidate for the current standard of care treatment. VLA009B: locally advanced and/or metastatic disease and judged to be a candidate for pembrolizumab to be used in combination with CVA21.Xx_NEWLINE_xXInclusion Criteria:\n\n        Among other criteria, patients must meet all of the following conditions to be eligible for\n        the study:\n\n          1. Diagnosed with metastatic (i.e., cancer that has spread) TNBC\n\n               -  minimal or no expression of estrogen and progesterone receptors (ER/PR) <10% of\n                  cells positive by immunohistochemistry\n\n               -  HER 2 staining 0 or 1+ by IHC or copy number <4.0 signals/cell\n\n          2. Documented progression of disease based on radiographic, clinical or pathologic\n             assessment during or subsequent to the last anticancer regimen received.\n\n          3. Breast cancer tumor confirmed to express gpNMB. This will be determined by submitting\n             a tissue sample from the advanced (locally advanced/recurrent or metastatic) disease\n             setting to a central laboratory for analysis.\n\n          4. Received no more than two prior chemotherapy treatments for advanced (locally\n             advanced/recurrent or metastatic) breast cancer.\n\n          5. Prior chemotherapy treatment must have contained an anthracycline (e.g. doxorubicin or\n             Doxil) if clinically indicated and a taxane (eg: Taxol).\n\n          6. ECOG performance status of 0 - 1.\n\n          7. Adequate bone marrow, liver and renal function.\n\n        Exclusion:\n\n        Among other criteria, patients who meet any of the following conditions are NOT eligible\n        for the study:\n\n          1. Progression/recurrence of breast cancer during or within 3 months of completion of\n             neoadjuvant or adjuvant chemotherapy.\n\n          2. Ongoing neuropathy or other chemotherapy or radiation-related toxicities that are\n             moderate (Grade 2) or worse in severity.\n\n          3. Known brain metastases, unless previously treated and asymptomatic for 2 months and\n             not progressive in size or number for 2 months.\n\n          4. Significant cardiovascular disease.\n\n          5. Previously received capecitabine and discontinued due to progression or intolerance;\n             previously received CDX-011 or other MMAE containing agents.\n\n          6. Active systemic infection requiring treatment. Infection controlled by oral therapy\n             will not be exclusionary.\n\n          7. Chronic use of systemic corticosteroids.Xx_NEWLINE_xXSubjects with recurrent, locally advanced unresectable or metastatic adenocarcinoma of the pancreas who have progressed after primary therapy with FOLFIRINOX or FOLFIRINOX-like regimen or were intolerant of it.Xx_NEWLINE_xXHistologically or cytologically confirmed invasive BC: incurable, unresectable, locally advanced BC previously treated with multimodality therapy or metastatic BCXx_NEWLINE_xXPrior treatment for BC in the: adjuvant; unresectable locally advanced; or metastatic settings; which must include both, a taxane and trastuzumab (alone or in combination with another agent)Xx_NEWLINE_xXProgression must have occurred during or after most recent treatment for locally advanced/metastatic BC or within 6 months after completing adjuvant therapyXx_NEWLINE_xXPrior systemic therapy and chemoradiotherapy for treatment of resectable, borderline resectable or locally advanced unresectable disease is allowed and does not count toward prior therapy for metastatic diseaseXx_NEWLINE_xXPatients who received systemic therapy with gemcitabine/nab-paclitaxel for resectable or borderline/locally advanced unresectable disease and progressed with metastatic disease within 3 months of the past dose of systemic therapy are eligibleXx_NEWLINE_xXHas locally advanced/metastatic disease (i.e., newly diagnosed Stage IV RCC per American Joint Committee on Cancer) or has recurrent disease.Xx_NEWLINE_xXPresence of advanced malignant hepatic tumors.Xx_NEWLINE_xXHistologically confirmed locally advanced or stage IV NSCLCXx_NEWLINE_xXNo more than 2 prior chemotherapies in the advanced or metastatic settingXx_NEWLINE_xXDiagnosis of locally advanced or metastatic RCC that is predominantly clear cell histologyXx_NEWLINE_xXPresence of histologically confirmed inoperable locally advanced or metastatic pancreatic adenocarcinomaXx_NEWLINE_xXFor Dose Escalation (Part A): The participant must have histological or cytological evidence of cancer, either a solid tumor or a lymphoma, which is advanced or metastatic.Xx_NEWLINE_xXReceipt of prior systemic anti-cancer therapy for unresectable, locally advanced or metastatic melanomaXx_NEWLINE_xXPreviously received more than 1 regimen of systemic anticancer therapy for locally advanced or metastatic disease.Xx_NEWLINE_xXAdults with histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction that is inoperable, locally advanced or metastatic and not amenable to curative therapyXx_NEWLINE_xXPrevious chemotherapy for locally advanced or metastatic gastric cancer.Xx_NEWLINE_xXMetastatic disease or locally advanced, unresectable disease.Xx_NEWLINE_xXInclusion Criteria - Cohort Expansion Phase:\n\n          -  Histologically-proven, unresectable, locally advanced or metastatic melanoma or NSCLC\n\n               -  Melanoma: Advanced or metastatic melanoma patients may be systemic therapy naïve\n                  or may have received systemic treatment for unresectable locally advanced or\n                  metastatic disease. A patient who previously received systemic therapy must have\n                  had progression on a checkpoint inhibitor (e.g., anti-PD-L1, anti-PD-1,\n                  anti-CTLA-4) as the most recent prior therapy.\n\n               -  NSCLC: NSCLC that has progressed during or following 1 or more prior systemic\n                  therapies for unresectable locally advanced or metastatic disease. Patients who\n                  are intolerant of, or have refused treatment with standard first line cancer\n                  therapy, will be allowed to enroll. Patients must not have had more than 5 prior\n                  systemic regimens (excluding experimental therapies) for unresectable locally\n                  advanced or metastatic disease.\n\n          -  B7-H3 expression is not required for eligibility in this study; however, tumor\n             expression of B7-H3 will be evaluated for all patients.\n\n          -  Measurable disease per RECIST 1.1 criteria\n\n          -  ECOG performance status 0 or 1\n\n          -  Acceptable laboratory parameters and adequate organ reserve.\n\n        Exclusion Criteria - Cohort Expansion Phase:\n\n          -  Patients with a history of symptomatic central nervous system metastases, unless\n             treated and asymptomatic\n\n          -  Patients with history of autoimmune disease with certain exceptions\n\n          -  History of allogeneic bone marrow, stem cell, or solid organ transplant\n\n          -  Treatment with systemic cancer therapy or investigational therapy within 4 weeks;\n             radiation within 2 weeks; trauma or major surgery within 4 weeks\n\n          -  History of clinically-significant cardiovascular disease; gastrointestinal\n             perforation; gastrointestinal bleeding, acute pancreatitis or diverticulitis within 4\n             weeks;\n\n          -  Active viral, bacterial, or systemic fungal infection requiring parenteral treatment\n             within 7 days; positive for human immunodeficiency virus or AIDS, hepatitis B or C.\n\n          -  Known hypersensitivity to recombinant proteins, polysorbate 80, or any excipient\n             contained in the drug or vehicle formulation for MGA271 or ipilimumab.Xx_NEWLINE_xXPostmenopausal women with histologically or cytologically confirmed locally advanced or metastatic ER positive breast cancerXx_NEWLINE_xXPatients with locally advanced unresectable pancreatic ductal adenocarcinoma are excluded.Xx_NEWLINE_xXRadiographic and pathologic staging consistent with pancreatic cancer, locally advanced, unresectable (per NCCN criteria)Xx_NEWLINE_xXLaparoscopic confirmation that PDAC is locally advanced. Biliary stents are permittedXx_NEWLINE_xXThe subject has metastatic disease or has locally advanced disease that is not amendable to curative treatmentXx_NEWLINE_xXThe subject has received at least 1 line of therapy in the metastatic or locally advanced disease setting. The subject has been documented to have progressed by determination of the investigator on a regimen containing an anti-HER2 agent as the most recent regimen or the most recent anti-HER2 regimen was discontinued for any toxicity, with the exception of a cardiotoxicity.Xx_NEWLINE_xXAdult women (? 18 years of age) with metastatic or locally advanced breast cancerXx_NEWLINE_xXProgression while on, or within one month of end of letrozole or anastrozole treatment for locally advanced or metastatic breast cancer.Xx_NEWLINE_xXHave received no prior systemic chemotherapy for advanced/unresectable (inoperable) or metastatic urothelial cancer.Xx_NEWLINE_xXHistologic confirmation of locally advanced or metastatic RCC with a clear-cell component with or without sarcomatoid features.Xx_NEWLINE_xXNasopharyngeal carcinoma basket\r\n* Metastatic or locally recurrent disease not amenable to curative intent treatment\r\n* Any number of prior therapies, including 0Xx_NEWLINE_xXMerkel cell carcinoma basket \r\n* Metastatic or locally recurrent disease not amenable to curative intent treatment\r\n* Any number of prior therapies, including 0Xx_NEWLINE_xXHistologically or cytologically confirmed breast cancer with evidence of metastatic or locally advanced disease not amenable to resection or radiation therapy with curative intent and who have progressed during treatment with at least one prior hormonal therapyXx_NEWLINE_xXHistologically confirmed inoperable locally advanced or metastatic adenocarcinoma of the stomach or GEJ which have progressed on at least 1 prior systemic therapy or line of treatment for unresectable/metastatic diseaseXx_NEWLINE_xXSubjects must have histologically confirmed, locally advanced or metastatic solid cancers of the following histological types:Xx_NEWLINE_xXhistopathologically confirmed advanced or metastatic colorectal cancer, excluding primary tumors of appendiceal originXx_NEWLINE_xXEvidence that the renal cell carcinoma is advanced or metastatic.Xx_NEWLINE_xXPrevious systemic therapy for locally advanced or metastatic disease is not allowed.Xx_NEWLINE_xXLocally recurrent/metastaticXx_NEWLINE_xXHistologically or cytologically documented, locally advanced or metastatic solid tumour, excluding lymphoma, for which standard therapy does not exist or has proven ineffective or intolerable.Xx_NEWLINE_xXLocally advanced, recurrent, or metastatic incurable solid malignancy with measurable disease per RECIST v1.1Xx_NEWLINE_xXHistologically-confirmed, locally advanced or metastatic adenocarcinoma of the breastXx_NEWLINE_xXPatient has advanced (loco regionally recurrent not amenable to curative therapy, e.g. surgery and/or radiotherapy, or metastatic) breast cancer. Patients may be:Xx_NEWLINE_xXPatients with histological or cytological proven diagnosis of adenocarcinoma of the breast with evidence of either locally advanced, inoperable and/or metastatic diseaseXx_NEWLINE_xXPatient has advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapyXx_NEWLINE_xXIn the phase Ib portion, must have locally advanced or metastatic GIST and have progressed on imatinibXx_NEWLINE_xXPatients with metastatic cancer and/or cancer that is not amenable to surgery (i.e. must be curative intent; locally advanced is acceptable)Xx_NEWLINE_xXPatients must have histologically or cytologically documented adenocarcinoma of the colon or rectum that is either metastatic, or locally advanced and unresectable; NOTE: in the event that both cecal and appendiceal primaries are considered, patient is eligible if it is concluded by the treating oncologist to most likely be cecal based on pathological, surgical, and clinical interpretationXx_NEWLINE_xXHistologically documented triple-negative adenocarcinoma of the breast that is inoperable locally advanced or metastatic and is not amenable to resection with curative intentXx_NEWLINE_xXAny previous therapy, including chemotherapy or hormonal or targeted therapy, for inoperable locally advanced or metastatic triple-negative adenocarcinoma of the breast. Participants may have received prior neoadjuvant or adjuvant chemotherapy and/or radiation treatment for locally advanced triple negative adenocarcinoma, provided all treatments were completed greater than or equal to (>/=) 6 months prior to Cycle 1 Day 1. Locally recurrent disease must not be amenable to resection with curative intentXx_NEWLINE_xXHistologically or cytologically proven diagnosis of adenocarcinoma of the breast with evidence of locally recurrent disease not amenable to resection or radiation therapy with curative intent, or metastatic disease.Xx_NEWLINE_xXPrior treatment with any type of systemic therapy for advanced disease.Xx_NEWLINE_xXFor Part A (abemaciclib + pemetrexed): Non-squamous subtypes only. The participant must have received at least one but no more than three prior therapies for advanced/metastatic NSCLC.Xx_NEWLINE_xXFor Part B (abemaciclib + gemcitabine): Any subtype. The participant must have received at least one but not more than three prior therapies for advanced/metastatic NSCLC.Xx_NEWLINE_xXFor Part C (abemaciclib + ramucirumab): Any subtype. The participant must have received at least two but not more than three prior therapies for advanced/metastatic NSCLC.Xx_NEWLINE_xXFor Part E (abemaciclib + pembrolizumab): Any subtype. The participant must have received at least one but no more than three prior therapies for advanced/metastatic NSCLC.Xx_NEWLINE_xXStage IV or locally advanced cancers for which no alternative therapies with proven survival advantage are availableXx_NEWLINE_xXLocally advanced and/or metastatic diseaseXx_NEWLINE_xXMay have received prior therapies for advanced or metastatic diseaseXx_NEWLINE_xXWomen 18 years or older with metastatic or locally advanced disease, not amenable to curative therapyXx_NEWLINE_xXBiopsy-proven and inoperable locally advanced, recurrent, or metastatic cancer of the esophagus, stomach, or gastro-esophageal junction – adenocarcinoma typeXx_NEWLINE_xXMetastatic or locally advanced disease that is not amenable to resection or radiation with curative intent.Xx_NEWLINE_xXOther anticancer therapy for locally advanced or metastatic breast cancer except for prior hormonal therapy.Xx_NEWLINE_xXLocally advanced (T4b, any N; any T, N2-3) or metastatic (M1) disease as determined by the treating investigatorXx_NEWLINE_xXHistologic or cytologic evidence of a malignant solid tumor or lymphoma (any histology) and must have advanced disease, defined as cancer that is either metastatic or locally advanced and unresectable (and for which additional radiation therapy or other locoregional therapies are not considered feasible).Xx_NEWLINE_xXHistological or cytological diagnosis of metastatic cancer or locally advanced cancer that is not amenable to local therapyXx_NEWLINE_xXHistologically-proven locally advanced or metastatic solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma who is no longer benefiting from standard anti-cancer treatment or for whom, in the opinion of the treating physician, no such treatment is available or indicatedXx_NEWLINE_xXHistologically-proven, unresectable, locally advanced or metastatic melanoma, SCCHN, NSCLC, and other cancers that express B7-H3.Xx_NEWLINE_xXMelanoma that has progressed during or following at least 1 and up to 5 prior systemic treatments for unresectable locally advanced or metastatic disease, or melanoma patients who are intolerable of or have refused standard cancer therapy. Pre- and on-study biopsy required.Xx_NEWLINE_xXSubjects with cytologically or histologically confirmed locally advanced or metastatic solid tumor malignancyXx_NEWLINE_xXIn the phase I dose escalation study, must have locally advanced, unresectable or metastatic GIST and have progressed on imatinibXx_NEWLINE_xXConcurrent active inoperable locally advanced or metastatic malignancy (other than malignancies, which the investigator determines are unlikely to interfere with treatment and safety analysis or are less of a treatment priority than their diagnosis of advanced GIST)Xx_NEWLINE_xXPatients must have advanced or recurrent disease that is refractory to curative treatment based on imaging or clinical exam.Xx_NEWLINE_xXLocally advanced unresectable pancreatic cancer by National Comprehensive Cancer Network (NCCN) criteriaXx_NEWLINE_xXHistologically confirmed diagnosis of a locally advanced or metastatic solid tumor.Xx_NEWLINE_xXMetastatic or locally recurrent TNBCXx_NEWLINE_xXPatients must have a histologically confirmed stage IV or unresectable locally advanced adrenocortical carcinomaXx_NEWLINE_xXReceived and failed, or were intolerant to, at least 1 prior systemic therapy for locally advanced or metastatic pancreatic ductal adenocarcinoma.Xx_NEWLINE_xXUnresectable locally advanced or metastatic MPM after locally confirmed progression on 1st line treatment with platinum in combination with pemetrexed.Xx_NEWLINE_xXLocally unresectable or metastatic carcinoid or pNETXx_NEWLINE_xXMeasurable metastatic disease or locally advanced and unresectable diseaseXx_NEWLINE_xXHistologically or cytologically confirmed locally advanced or metastatic colon or rectal adenocarcinomaXx_NEWLINE_xXSubject has a documented diagnosis of advanced HCC of any etiology.Xx_NEWLINE_xXPatients must have histological or cytological diagnosis of melanoma with progressive locally advanced or metastatic disease that is not amenable to definitive local therapy with curative intentXx_NEWLINE_xXLocally advanced (clearly unresectable) or metastatic diseaseXx_NEWLINE_xXCytologically or histologically confirmed adenocarcinoma of locally advanced or metastatic NSCLC which is not amenable to curative surgery or radiotherapyXx_NEWLINE_xXHistologically-proven locally advanced unresectable or metastatic high colorectal carcinomaXx_NEWLINE_xXLocally advanced/metastatic NSCLC, not amenable to curative surgery or radiotherapyXx_NEWLINE_xXMust have locally advanced or distant metastatic disease that is not surgically curableXx_NEWLINE_xXPatients may have received up to one prior line of chemotherapy for metastatic or unresectable locally advanced breast cancerXx_NEWLINE_xXThe participant received >1 line of prior therapy for the treatment of locally advanced and unresectable or metastatic gastric or GEJ (Siewert Types I-III) adenocarcinoma.Xx_NEWLINE_xXSubjects can be treatment naive for metastatic or incurable locally advanced HPV-16 positive solid tumors or can have one prior line of treatmentXx_NEWLINE_xXPatients diagnosed with advanced melanomaXx_NEWLINE_xXi) With at least 1 platinum-containing chemotherapy regimen for metastatic or surgically unresectable locally advanced urothelial cancer, orXx_NEWLINE_xXConfirmed metastatic or locally advanced, unresectable disease (by computed tomography [CT] scan or clinical evidence)Xx_NEWLINE_xXNo prior systemic therapy administered in the recurrent or metastatic setting (with the exception of systemic therapy completed > 6 months prior if given as part of multimodal treatment for locally advanced disease)Xx_NEWLINE_xXHistologically or cytologically documented locally advanced or metastatic UBC (including renal pelvis, ureters, urinary bladder, and urethra)Xx_NEWLINE_xXDisease progression during or following treatment with at least one platinum-containing regimen for inoperable, locally advanced or metastatic UBC or disease recurrenceXx_NEWLINE_xXLocally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy.Xx_NEWLINE_xXPrior treatment with any systemic anti-cancer therapy for locally advanced/metastatic NSCLC.Xx_NEWLINE_xXMetastatic or locally advanced (unresectable) colorectal cancer with histological confirmation of adenocarcinomaXx_NEWLINE_xXHistologically or cytologically confirmed locally advanced adenocarcinoma of the pancreas that is considered unresectable or borderline resectable based on institutional standardized criteria of unresectability or medical inoperability; patients with and without regional adenopathy are eligibleXx_NEWLINE_xXPhase I: patients with any locally advanced or metastatic gastrointestinal malignancy which mFOLFOX6 is indicated for treatmentXx_NEWLINE_xXHistologic proof of metastatic or locally advanced, unresectable breast cancer which is estrogen receptor positive and/or progesterone positive per institutional standardsXx_NEWLINE_xXPatients must have locally advanced or metastatic predominantly urothelial carcinoma of the bladder, ureter, or urethra that is not amenable to curative surgical treatmentXx_NEWLINE_xXLocally advanced or metastatic NSCLCXx_NEWLINE_xXPatients must have an unresectable locally advanced or metastatic adenocarcinomaXx_NEWLINE_xXPatients whose esophageal or GEJ cancer has become metastatic or unresectable locally advanced within 6 months of completing definitive therapy for localized or locally advanced cancer can be considered as having received one line of therapy for advanced cancerXx_NEWLINE_xXHistologically confirmed PRCC, which is locally advanced or metastatic.Xx_NEWLINE_xXDocumented evidence of NSCLC (locally advanced, unresectable, Stage III)Xx_NEWLINE_xXPatients must have histologically or cytologically documented carcinoma primary to the intra- or extra-hepatic biliary system or gall bladder with clinical and/or radiologic evidence of unresectable, locally advanced or metastatic disease; patients with ampullary carcinoma are not eligibleXx_NEWLINE_xXHistologically or cytologically documented locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, urethra)Xx_NEWLINE_xXDisease progression during or following treatment with at least one platinum-containing regimen (e.g., gemcitabine and cisplatin [GC], methotrexate, vinblastine, doxorubicin, and cisplatin [MVAC], CarboGem, etc.) for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence.Xx_NEWLINE_xXHave locally advanced disease not amenable to curative treatment by surgery or metastatic disease. In addition, participants must fulfill 1 of the following criteria:Xx_NEWLINE_xXPatients with advanced malignant solid tumors are excludedXx_NEWLINE_xXSubjects must have a. In the escalation phase, locally advanced or metastatic NSCLC subjects who have either failed to respond or relapsed following any line of standard treatment, were unable to tolerate, or were not eligible for standard treatment b. In the expansion phase, histologically or cytologically confirmed locally advanced or metastatic NSCLC that is EGFR mutation positive, naïve to EGFR TKI therapy, and sensitive to EGFR TKIs therapyXx_NEWLINE_xXDose Expansion: Chondrosarcoma a. Subjects must have IDH1 gene-mutated chondrosarcoma that is either locally advanced or metastatic and not amenable to complete surgical excision.Xx_NEWLINE_xXBiopsy proven locally advanced stage cervical cancer (LACC, International Federation of Gynecology and Obstetrics [FIGO] IB2 – IVB)Xx_NEWLINE_xXPHASE I: Patients may not have received > 2 prior chemotherapies for advanced diseaseXx_NEWLINE_xXAdvanced or metastatic cancerXx_NEWLINE_xXHistologically confirmed, locally advanced (T4 primary tumor and stage IIIB or IIIC disease) or metastatic breast cancer that progressed after treatment with standard treatment regimens in the adjuvant or neoadjuvant settingXx_NEWLINE_xXSolid tumor that is metastatic, locally advanced or recurrentXx_NEWLINE_xXWomen with advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.Xx_NEWLINE_xXNo prior systemic anti-cancer therapy for advanced disease.Xx_NEWLINE_xXPatients must have a histologically confirmed diagnosis of metastatic or locally advanced, unresectable:\r\n* Soft tissue sarcomas (non-liposarcoma)\r\n* Osteosarcoma\r\n* Liposarcoma-high grade, de-differentiated, or myxoid\r\n* Note: pathology is not required to be reviewed at the treating institution; a copy of the pathology report is sufficient for eligibility purposesXx_NEWLINE_xXCohort 1: Patients must have had a minimum of 1 and a maximum of 4 prior chemotherapy regimens for recurrent/metastatic disease or locally advanced/unresectable disease; it will be up to the investigator to determine what constitutes a “regimen” in each case; Cohort 2: Patients must have had a minimum of 1 and maximum of any number of prior chemotherapy regimens for recurrent/metastatic disease or locally advanced/unresectable disease; Cohort 3: Patients may have had any number of prior therapies for recurrent/metastatic or locally advanced/unresectable disease; there are no restrictions; all cohorts: The last dose of systemic therapy much have been given at least 28 days prior to initiation of therapy; patients receiving carmustine (BCNU) or mitomycin C must have received their last dose at least 6 weeks prior to initiation of therapyXx_NEWLINE_xXPatients with advanced malignant hepatic tumors (metastasis)Xx_NEWLINE_xXCohort A: patients with histologically proven metastatic or locally advanced MSI colorectal adenocarcinomaXx_NEWLINE_xXCohort B: patients with histologically proven metastatic or locally advanced microsatellite stable (MSS) colorectal adenocarcinomaXx_NEWLINE_xXCohort C: patients with histologically proven metastatic or locally advanced non-colorectal MSI solid tumor malignanciesXx_NEWLINE_xXCohort D: Patients with histologically proven metastatic or locally advanced solid tumor malignancies that are microsatellite stable with a documented mutation burden level measured at > 20 mutations per megabase pairs (MB)Xx_NEWLINE_xXLocally advanced or metastatic and/or unresectable Hepatocellular Carcinoma (HCC)Xx_NEWLINE_xXMust have histological or cytological confirmed diagnosis of locally advanced or metastatic adenocarcinoma of the pancreas, which has progressed on or after one line of chemotherapyXx_NEWLINE_xXInclusion Criteria for Dose Escalation:\n\n          -  Histologically or cytologically proven diagnosis of adenocarcinoma of the breast with\n             evidence of either locally recurrent disease not amenable to resection or radiation\n             therapy with curative intent or with metastatic disease\n\n          -  ER-positive tumor\n\n          -  HER2-negative breast cancer as per local laboratory testing\n\n          -  Measurable disease, or evaluable bone disease; that is, bone lesions that are lytic or\n             mixed (lytic + sclerotic) in the absence of measurable lesion\n\n          -  Required paired pre- and on-treatment tumor biopsies for participants with metastases\n             that are safely accessible as determined by the investigator\n\n          -  Advanced or metastatic ER-positive/HER2-negative breast cancer that has recurred or\n             progressed while being treated with adjuvant endocrine therapy for a duration of at\n             least 24 months and/or endocrine therapy in the incurable, locally advanced, or\n             metastatic setting and derived a clinical benefit from therapy (i.e., tumor response\n             or stable disease for at least 6 months)\n\n          -  No more than 2 prior lines of treatment for advanced or metastatic breast cancer\n\n          -  ? 2 weeks must have elapsed from the use of any other endocrine, targeted therapy or\n             chemotherapy\n\n          -  Cohort B0: No prior treatment with Cyclin-Dependent Kinase (CDK) 4/6 inhibitor\n\n          -  For participants undergoing 18F-fluoroestradiol (FES) positron emission tomography\n             (PET) imaging additional restrictions on prior therapy include: ? 2 months must have\n             elapsed from the use of tamoxifen; ? 6 months must have elapsed from the use of\n             fulvestrant\n\n          -  Postmenopausal status\n\n          -  Eastern Cooperative Oncology Group (ECOG) Performance Status ? 1\n\n          -  Resolution of all acute toxic effects of prior therapy or surgical procedures to\n             baseline or Grade ? 1 (except alopecia or other toxicities not considered to be a\n             safety risk for the patient)\n\n          -  Life expectancy of ? 12 weeks\n\n          -  Adequate organ function\n\n        Inclusion Criteria for Dose Expansion:\n\n        Same as above, except:\n\n          -  No more than one prior line of treatment for advanced or metastatic breast cancer\n\n          -  Advanced or metastatic disease that is either refractory to or intolerant of existing\n             standard therapy or for which no effective standard therapy that confers clinical\n             benefit is available\n\n        And plus:\n\n          -  Cohort B1?2: No prior treatment with CDK4/6 inhibitor\n\n          -  Cohorts A1, A3, and B1 only: Postmenopausal status\n\n          -  Cohorts A2, A4, and B2 only: Participants not defined as post-menopausal\n\n          -  No prior treatment with an oral selective estrogen receptor degrader (SERD)\n\n          -  For women of childbearing potential: agreement to remain abstinent (refrain from\n             heterosexual intercourse) or use non-hormonal contraceptive methods with a failure\n             rate of < 1% per year during the treatment period and for 40 days after the last dose\n             of GDC-9545\n\n        Exclusion Criteria for Dose Escalation:\n\n          -  Known brain metastases that are untreated, symptomatic, or require therapy to control\n             symptoms.\n\n          -  Current treatment with any systemic anti-cancer therapies for advanced disease\n\n          -  Concurrent treatment with warfarin or phenytoin\n\n          -  Diagnosis of any secondary malignancy within 3 years prior to enrollment, except for\n             appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or\n             Stage I uterine cancer\n\n          -  Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major\n             upper GI surgery including gastric resection\n\n          -  Known Human Immunodeficiency Virus (HIV) infection\n\n          -  Known clinically significant history of liver disease consistent with Child-Pugh Class\n             B or C, including active viral or other hepatitis (e.g., hepatitis B or hepatitis C\n             virus), current alcohol abuse, or cirrhosis\n\n          -  Major surgery within 4 weeks prior to enrollment\n\n          -  Radiation therapy within 2 weeks prior to enrollment\n\n        Exclusion Criteria for Dose Expansion:\n\n        Same as above, plus:\n\n          -  Pregnant, lactating, or breastfeeding\n\n          -  Additional exclusion criteria for participants in Cohort B: History of venous\n             thromboembolic event requiring therapeutic anticoagulationXx_NEWLINE_xXHistological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors that are not amenable for treatment with curative intent in adult patients with: NSCLC, TNBC, HR+ breast cancer, recurrent platinum sensitive ovarian cancer, UC, CRPC, and other advanced solid tumors with a BRCA or ATM gene defectXx_NEWLINE_xXHistological or cytological confirmation of locally advanced or metastatic NSCLC (IIIB-IV)Xx_NEWLINE_xXAny previous systemic chemotherapy treatment, extensive radiotherapy or investigational agent other than immunotherapy, or patients who have received more than one line of immunotherapy for locally advanced unresectable or metastatic melanoma; Ipilimumab (adjuvant) or other immunotherapy treatment must have ended at least 6 weeks prior to randomizationXx_NEWLINE_xXWilling and able to consent for biopsy of locally-advanced or metastatic breast cancer prior to treatmentXx_NEWLINE_xXMetastatic or locally advanced unresectable breast cancer (includes metastatic or locally advanced unresectable breast cancer which is diagnosed while on adjuvant letrozole or exemestane)Xx_NEWLINE_xXLocally unresectable or metastatic carcinoid tumorsXx_NEWLINE_xXHistologically and cytologically proven locally advanced or metastatic pancreatic adenocarcinoma that is not amenable to surgery, radiation, or combined modality therapy with curative intent, and has failed or is not eligible for available chemotherapiesXx_NEWLINE_xXPatients must have borderline resectable or locally advanced unresectable pancreatic cancer with no metastatic spread as determined by a baseline diagnostic CT scan with intravenous contrast (or MRI). CT should be performed according to a defined pancreas protocol such as triphasic cross-sectional imaging with thin slices. Optimal multi-phase technique including a non-contrast phase plus arterial, pancreatic parenchymal and portal venous phase of contrast enhancement with thin cuts (3mm) throughout the abdomen is preferred. Studies must be evaluated by a radiologist and/or surgeon and deemed borderline resectable or locally advanced unresectable as defined per the NCCN Practice Guidelines in Oncology V2.2012, as:Xx_NEWLINE_xXPatient has stage IIIB or IV diagnosis and must have received one or two prior regimens (including platinum- doublet) of cytotoxic chemotherapy for the treatment of locally advanced or metastatic NSCLC.Xx_NEWLINE_xXPatients must have received previous treatment with crizotinib for the treatment of locally advanced or metastatic NSCLC.Xx_NEWLINE_xXSubjects must have metastatic or locally advanced, unresectable cancer; cancer must be “active” (i.e. demonstrable by physical examination, blood tests, or radiographical procedures)Xx_NEWLINE_xXPK expansion patients: Histologic documentation of locally unresectable or metastatic renal cell carcinoma not currently amenable to surgery, radiation, or other therapy with curative intentXx_NEWLINE_xXPrevious cytotoxic chemotherapy for advanced (metastatic) diseaseXx_NEWLINE_xXNaïve untreated patients or patients who have progressed on or after any number of prior lines of immunotherapy for unresectable locally advanced or metastatic melanomaXx_NEWLINE_xXPrevious systemic chemotherapy for unresectable locally advanced or metastatic melanoma.Xx_NEWLINE_xXHistological or cytological confirmation of locally advanced or metastatic NSCLC (IIIB-IV)Xx_NEWLINE_xXPatients with metastatic or locally advanced, unresectable breast cancer not amenable to curative treatment by surgery or radiotherapyXx_NEWLINE_xXSubjects with histologically or cytologically-documented non-squamous cell NSCLC who present with Stage IIIB/IV disease or recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection, or definitive chemoradiation therapy for locally advanced disease) and who will receive study therapy as second or third line of treatment for advanced diseaseXx_NEWLINE_xXAdvanced/metastatic RCCXx_NEWLINE_xXReceived 1 or 2 prior anti-angiogenic therapy regimens in advanced or metastatic settingXx_NEWLINE_xXPatients with borderline resectable, locally advanced or metastatic disease.Xx_NEWLINE_xXPatients must have histologically confirmed adenocarcinoma of colorectal origin that is metastatic or locally advanced and unresectableXx_NEWLINE_xXPatients must not have received any prior systemic therapy for metastatic or locally advanced colorectal cancer (CRC); prior VEGF inhibitors are not allowedXx_NEWLINE_xXAmendment (January 2014): only subjects with the following histologies will be eligible\r\n* Cohort # 1 (pancreatic cohort): locally advanced or metastatic pancreatic adenocarcinoma\r\n* Cohort #2 (biliary tract cohort): locally advanced or metastatic cholangiocarcinoma, gall bladder adenocarcinoma, or ampullary carcinoma; patients with adenocarcinoma of unclear primary that are most likely of biliary tract origin (in the opinion of the treating physician) will also be allowed on this cohortXx_NEWLINE_xXSubjects must have metastatic and/or locally advanced or locally recurrent disease that is not amenable to curative surgical resection; If a patient declines surgery, they may be considered for this studyXx_NEWLINE_xXPresence of metastasized or locally advanced, inoperable (curative intent) at enrollment time, histologically proven, midgut carcinoid tumour (to be centrally confirmed).Xx_NEWLINE_xXPatients with clinical evidence of locally advanced, nodal, or metastatic bladder cancerXx_NEWLINE_xXPatients whose tumors are defined as locally advanced cancer or metastatic cancer are not eligibleXx_NEWLINE_xXPatients may have received up to one prior line of chemotherapy for metastatic or unresectable locally advanced breast cancerXx_NEWLINE_xXPatients with advanced malignant hepatic tumorsXx_NEWLINE_xXParticipants must have histologically confirmed adenocarcinoma of the colon or rectum that is metastatic or locally advanced (unresectable); patients with resected primary tumors who have documented metastases are eligible; documentation of residual disease by computed tomography (CT) scan or surgeon’s notes is required for all patients, and histologic confirmation of metastases is strongly encouragedXx_NEWLINE_xXWritten consent from Female or male patients aged 18 years and over. Previously confirmed histological diagnosis of unresectable, locally advanced or metastatic, hereditary or sporadic MTC Objective disease progression within the previous 14 months prior to enrolment, and/orXx_NEWLINE_xXParticipants with HER2-positive and hormone receptor-positive advanced metastatic or locally advanced breast cancerXx_NEWLINE_xXPrevious systemic non-hormonal anticancer therapy in the metastatic or locally advanced breast cancer settingXx_NEWLINE_xXParticipants must have histologically or cytologically confirmed locally advanced or metastatic pancreatic adenocarcinomaXx_NEWLINE_xXAdvanced or metastatic diseaseXx_NEWLINE_xXPatients with cytologically or histologically confirmed recurrent locally advanced or metastatic NSCLC have received at least one prior recognized systemic therapy for therapy for advanced disease, (recognized therapy must include a platinum doublet unless contraindicated due to organ dysfunction)Xx_NEWLINE_xXDose Expansion phase: Metastatic melanoma (locally advanced or metastatic melanoma)Xx_NEWLINE_xXAdvanced renal cell carcinoma of non-clear cell histology with papillary features, histologically confirmed by Memorial Sloan-Kettering Cancer Center (MSKCC) pathology; advanced disease is defined as unresectable, locally recurrent disease or metastatic disease; availability of additional tissue for correlative studies is NOT an inclusion requirementXx_NEWLINE_xXFor Dose Escalation (Part A): The participant must have histological or cytological evidence of cancer, either a solid tumor or a lymphoma, which is advanced and/or metastaticXx_NEWLINE_xXPart B: Non-small cell lung cancer of any subtype that is advanced and/or metastaticXx_NEWLINE_xXPart E: Melanoma that is advanced and/or metastaticXx_NEWLINE_xXHistologically documented (pathology confirmed at Memorial Sloan-Kettering Cancer Center [MSKCC]), incurable, locally advanced or metastatic solid tumor malignancy, lymphoma, or MPN; the safety-expansion phase will be open to accrual only for patients with MPNXx_NEWLINE_xXPathologic confirmation of metastatic or locally advanced RCC with a major clear cell componentXx_NEWLINE_xXLocally advanced/unresectable or metastatic breast cancerXx_NEWLINE_xXHistologically or cytologically proven diagnosis of unresectable B3 thymoma or thymic carcinoma recurrent or progressing after more than one prior systemic therapy for advanced / metastatic diseaseXx_NEWLINE_xXHistologically or cytologically confirmed diagnosis of metastatic or unresectable, locally advanced, recurrent NSCLC that has been previously treated (subjects who have failed adjuvant or locally advanced therapy within 6 months are also eligible to participate in the study)Xx_NEWLINE_xXEXPANSION COHORT ONLY: Metastatic or locally advanced unresectable urothelial carcinoma with histologic or cytologic confirmation at Dana-Farber Cancer Institute (DFCI) or Memorial Sloan-Kettering Cancer Center (MSKCC)Xx_NEWLINE_xXPatients must have measurable or non-measurable stage III/locally advanced or metastatic carcinoma of the breast where surgery is not possible; lesions must be evaluated within 4 weeks prior to registrationXx_NEWLINE_xXPatients must not have had more than 2 lines of non-hormonal treatment in the locally advanced or metastatic setting, including trastuzumab (Herceptin), bevacizumab, or other agents; treatment in the locally advanced or metastatic setting must have been completed at least 2 weeks prior to study registrationXx_NEWLINE_xXPrior aromatase inhibitors (e.g. anastrozole, letrozole, exemestane, aminoglutethamide) are allowed in the locally advanced or metastatic settingXx_NEWLINE_xXPrior tamoxifen is not allowed in the locally advanced or metastatic settingXx_NEWLINE_xXPatients who have received other agents that modulate or downregulate the estrogen receptor (e.g. raloxifene, fulvestrant) in the locally advanced or metastatic setting are eligible if they were on treatment for at least 6 months and must have discontinued these agents 6 months prior to study registrationXx_NEWLINE_xXHistologically- or cytologically-confirmed diagnosis of locally advanced/unresectable (inoperable or not amenable to surgical treatment) and/or metastatic transitional cell urothelial cancer of the renal pelvis, ureter, urinary bladder, or urethraXx_NEWLINE_xXHistologically or cytologically confirmed locally advanced, inoperable (where surgery is not indicated due to disease extension, co-morbidities, or other technical reasons), or metastatic iCCA or mixed histology tumors (combined hepatocellular-cholangiocarcinoma [cHCC-CCA])Xx_NEWLINE_xXHas histologically- or cytologically-confirmed diagnosis of locally advanced unresectable or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the esophagogastric junction (EGJ)Xx_NEWLINE_xXHas locally advanced esophageal carcinoma that is resectable or potentially curable with radiation therapy (as determined by local investigator)Xx_NEWLINE_xXHas had previous therapy for advanced/metastatic adenocarcinoma or squamous cell cancer of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the EGJXx_NEWLINE_xXCytologically or histologically and radiologically confirmed solid tumor that is inoperable, locally advanced, metastatic, or recurrent:Xx_NEWLINE_xXExpansion Cohort 5: Subjects with UC with transitional cell histology (including renal pelvis, ureter, urinary bladder, urethra) who have radiographically progressed on or after one prior immune check-point inhibitor (anti-PD1 or anti-PD-L1) as the most recent therapy for the treatment of inoperable, locally advanced, or metastatic disease.Xx_NEWLINE_xXHistologically confirmed Papillary Renal Cell Carcinoma, which is unresectable and locally advanced or metastatic with measurable disease as per RECIST 1.1.Xx_NEWLINE_xXIndication A - ASPS: Histologically proven, unresectable, locally advanced or metastatic alveolar soft part sarcoma.Xx_NEWLINE_xXIndication B - LMS: Histologically proven, unresectable, recurrent, locally advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular origin and of the bone).Xx_NEWLINE_xXIndication C - SS: Histologically proven, unresectable, recurrent, locally advanced or metastatic synovial sarcoma.Xx_NEWLINE_xXHistologically confirmed, chemo-refractory, locally advanced, recurrent or metastatic gastric (including GE junction), colorectal, or pancreatic adenocarcinoma.Xx_NEWLINE_xXAdvanced biopsy-proven metastatic non-small cell lung cancerXx_NEWLINE_xXHistologically confirmed advanced or metastatic non-curable solid tumor (if limited to a single lesion may not be a candidate for curative surgery or radiation therapy). Successful vaccine manufacture has resulted from tissue/fluid obtained from the following major organ systems: digestive, endocrine, reproductive, respiratory, and urinary.Individuals manufactured under CL-PTL 105 (Phase II Ovarian) may be eligible for enrollment without advanced or metastatic disease.Xx_NEWLINE_xXSurgically unresectable locally recurrent disease and/or metastatic disease following RAI ablation (if locally recurrent and ultrasound (US) positive, baseline FDG-PET or MRI will be obtained).Xx_NEWLINE_xXLocally advanced or metastatic solid tumors with the exception of primary brain tumor, and have failed standard of care therapyXx_NEWLINE_xXSubjects must have a pathologic diagnosis of advanced/metastatic urothelial cancer (carcinoma of the bladder, ureter, and/or renal pelvis) and must have failed at least 1 line of prior therapy in the metastatic/unresectable settingXx_NEWLINE_xXPrior systemic anti-cancer therapy other than endocrine therapy for locally recurrent or metastatic diseaseXx_NEWLINE_xXPatients with advanced malignant hepatic tumorsXx_NEWLINE_xXConfirmed diagnosis of unresectable, locally advanced or metastatic hereditary or sporadic Medullary Thyroid Cancer.Xx_NEWLINE_xXPatients must have locally advanced or metastatic urothelial cancer that is not amenable to surgical treatmentXx_NEWLINE_xXHas a diagnosis of locally advanced rectal or rectosigmoid cancer undergoing extended en bloc operations.Xx_NEWLINE_xXOnly locally advanced diseaseXx_NEWLINE_xXHistologically or cytologically confirmed advanced metastatic or unresectable advanced colorectal cancer (CRC) or gastric cancer that is relapsed, refractory, or progressive after:Xx_NEWLINE_xXPathologic diagnosis of solid tumor malignancy that is locally advanced or metastatic at time of Screening with documented HER2 expression.Xx_NEWLINE_xXHistologically or cytologically proved diagnosis of locally advanced recurrent or metastatic non-squamous NSCLC that is not suitable for local curative treatment.Xx_NEWLINE_xXLocally advanced HCCXx_NEWLINE_xXPatients must have documented locally advanced/metastatic disease, defined by the investigator, which is not amenable to resection with curative intent.Xx_NEWLINE_xXHistologically or cytologically confirmed metastatic or unresectable locally advanced/metastatic NSCLCXx_NEWLINE_xXAdvanced adenocarcinoma of the pancreas that is inoperable or metastatic.Xx_NEWLINE_xXReceived more than 1 prior regimen for advanced or metastatic disease.Xx_NEWLINE_xXAdvanced colorectal carcinoma.Xx_NEWLINE_xXPrior radiation to the pelvis or abdomen in the metastatic or locally advanced setting.Xx_NEWLINE_xXSubject has histologically confirmed locally advanced or unresectable Stage IIIB (not amenable to receive curative treatments such as chemo-radiation)/IV or metastatic NSCLC.Xx_NEWLINE_xXAdvanced (metastatic or locally advanced) serous epithelial ovarian, serous fallopian tubal or serous primary peritoneal cancer or advanced clear cell or papillary renal cell carcinoma who have received or are intolerant to all therapy known to confer clinical benefit for their disease, as determined by the investigator.Xx_NEWLINE_xXHas received prior systemic treatment with a taxane for advanced/metastatic diseaseXx_NEWLINE_xXPart 2: Subjects with histologically confirmed, locally advanced or refractory TGCT (including metastatic disease) that has been deemed unresectable by an orthopedic surgeon or similar qualified personnel.Xx_NEWLINE_xXPatients must have a clinical diagnosis of Birt-Hogg-Dube syndrome (clinical features consistent with BHD and /or a germline FLCN mutation) and the presence of localized, locally advanced or advanced, renal tumor(s)Xx_NEWLINE_xXSubject has histologically or cytologically confirmed metastatic or locally advanced, unresectable non-small-cell lung cancer (NSCLC).Xx_NEWLINE_xXNo more than three prior anticancer regimens (BRAF/MEK inhibitors, IL-2 or investigational agents) including no more than one chemotherapy-containing regimen for advanced (recurrent, locally advanced or metastic) disease.Xx_NEWLINE_xXAdvanced metastatic diseaseXx_NEWLINE_xXHistologically confirmed and documented previously treated Stage IIIB/IV NSCLC, having failed 1 previous platinum chemo regimen for locally advanced or metastatic disease.Xx_NEWLINE_xXFailed more than 3 treatment regimens for locally advanced or metastatic NSCLC.Xx_NEWLINE_xXMetastatic and/or locally advanced malignant solid tumors enriched in tumor types known to be mesothelin expressingXx_NEWLINE_xXPatients with locally advanced BCC are required to have disease that is considered inoperable due to significant functional compromise or to have a medical contraindication to surgeryXx_NEWLINE_xXPatients with nevoid BCC syndrome (Gorlin syndrome) may enroll in this study but must meet the criteria for locally advanced or metastatic disease listed aboveXx_NEWLINE_xXHistological or cytological diagnosis of triple negative breast cancer (TNBC) with evidence of a) metastatic or b) locally recurrent advanced disease that is not amenable to resection or radiotherapy with curative intent.Xx_NEWLINE_xXConfirmed diagnosis of: \r\n* Postmenopausal advanced hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer after failure of treatment with letrozole or anastrozole\r\n* Progressive neuroendocrine tumors of pancreatic origin (PNET) that is unresectable, locally advanced or metastatic\r\n* Advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenibXx_NEWLINE_xXSubject has definitive histologically or cytologically confirmed locally advanced unresectable or metastatic pancreatic adenocarcinoma (islet cell neoplasms are excluded) that is measurable by RECIST Version 1.1 guidelines.Xx_NEWLINE_xXHistological diagnosis of metastatic or locally advanced inoperable adenocarcinoma of the esophagus, gastroesophageal junction or stomachXx_NEWLINE_xXPatients must show signs of progression during or =< 4 months after being treated with a first line therapy for their metastatic or locally advanced inoperable cancerXx_NEWLINE_xXTreatment with 1 or more prior chemotherapies for advanced or metastatic adenocarcinoma of the pancreas.Xx_NEWLINE_xXTreatment with 1 or more prior chemotherapies for advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction.Xx_NEWLINE_xXReceived prior treatment with capecitabine or fluoropyrimidine for advanced or metastatic diseaseXx_NEWLINE_xXAdvanced adenocarcinoma of the pancreas that is inoperable or metastatic.Xx_NEWLINE_xXReceived more than 1 prior regimen for advanced or metastatic disease.Xx_NEWLINE_xXPrevious systemic therapy for advanced or metastatic disease.Xx_NEWLINE_xXNo prior chemotherapy for locally advanced or metastatic diseaseXx_NEWLINE_xXSubjects greater than or equal to (>=) 18 years of age with locally advanced unresectable or metastatic pancreatic adenocarcinoma proven by histology or cytology and previously untreated with chemotherapy or systemic therapy other than:Xx_NEWLINE_xXReceived at least two prior systemic cytotoxic chemotherapy regimens for unresectable, locally advanced or metastatic disease.Xx_NEWLINE_xXAt least one of the prior systemic cytotoxic chemotherapy regimens for unresectable, locally advanced or metastatic disease must have contained gemcitabine and have met the following criteria:Xx_NEWLINE_xXDiagnosis of locally advanced or metastatic liver cancer obtained by histology/cytology or by imagingXx_NEWLINE_xXDiagnosis of breast cancer with evidence of a) metastatic or b) locally recurrent/advanced disease.Xx_NEWLINE_xXDocumented disease progression during or following most first line therapy for advanced diseaseXx_NEWLINE_xXPatient has borderline resectable, locally advanced unresectable or advanced metastatic disease; patients with adenocarcinoma of the distal pancreatic body or tail are ineligible; patients with endocrine tumors, lymphoma of the pancreas, or ampullary cancer are also ineligibleXx_NEWLINE_xXPatient has localized resectable, locally advanced unresectable or advanced metastatic disease; patients with adenocarcinoma of the pancreatic body or tail are ineligibleXx_NEWLINE_xXMetastatic disease as documented by CT scan or MRI (locally advanced disease only NOT eligible)Xx_NEWLINE_xXFemales with a histologically confirmed diagnosis of breast cancer that is metastatic or locally advanced (locally advanced tumors must not be amenable to surgery or radiation therapy with curative intent) with the following pathological characteristics determined locally: estrogen receptor positive and Human Epidermal Growth Factor Receptor 2 (HER-2) negative, and Ki67 (a tumor marker) ? 15% determined by the central study laboratoryXx_NEWLINE_xXLocally advanced or inflammatory breast cancer (stage IIIA to IIIC)Xx_NEWLINE_xXPrevious chemotherapy for locally advanced or metastatic diseaseXx_NEWLINE_xXPANCREATIC CANCER COHORT (COHORT 4 ONLY): Subjects with recurrent, locally advanced unresectable or metastatic adenocarcinoma of the pancreas; the diagnosis will be confirmed by the Laboratory of Pathology/CCR/NCIXx_NEWLINE_xXEvidence of locally advanced, metastatic, muscle-invasive, and/or extravesical bladder cancerXx_NEWLINE_xXHistologically confirmed, unresectable locally advanced or metastatic transitional cell carcinoma of the urotheliumXx_NEWLINE_xXPart 2a, Part 2c, and Part 2f (GIST patients): Histologically confirmed locally advanced, metastatic and/or unresectable GIST.Xx_NEWLINE_xXLocally advanced or metastatic solid tumors;Xx_NEWLINE_xXPatient has locally recurrent or metastatic diseaseXx_NEWLINE_xXHistologic documentation of incurable, locally advanced, or metastatic pancreatic ductal adenocarcinoma consisting of unresectable pancreatic ductal adenocarcinoma (i.e., participants who are not considered eligible for surgical resection with curative intent), including recurrence of previously resected diseaseXx_NEWLINE_xXParticipants must have histological or cytological confirmed diagnosis of the following tumor types that is advanced and/or metastatic cancer and must be, in the judgment of the investigator, an appropriate participant for experimental therapyXx_NEWLINE_xXSubjects with histologically confirmed advanced primary endometrial cancer (locally advanced and incurable endometrial cancer that has been treated with surgery and/or radiation or is ineligible for such treatment), or recurrent or metastatic endometrial cancer, andXx_NEWLINE_xXHave advanced or metastatic cancer and be an appropriate candidate for experimental therapy.Xx_NEWLINE_xXHistologically or cytologically documented, locally advanced or metastatic solid tumors for which standard therapy either does not exist or has proven ineffective or intolerableXx_NEWLINE_xXNo more than four prior systemic therapies for locally advanced or metastatic cancerXx_NEWLINE_xXSubjects must have histologically or cytologically confirmed solid tumor malignancy that is unresectable/locally advanced and/or metastatic and for which standard curative or palliative measures are not available or are no longer effective (for all subjects, histologic or cytologic proof of malignancy based on prior primary cancer pathology is acceptable).Xx_NEWLINE_xXLocally advanced or inflammatory cervical or uterine cancerXx_NEWLINE_xXHistologically confirmed, locally advanced, not amenable to curative therapy, or metastatic non-small cell lung cancer (NSCLC)Xx_NEWLINE_xXParticipants must have a history of advanced gastric cancer (AGC), defined as\n             unresectable and locally advanced or metastatic gastric cancer, including\n             adenocarcinoma of the gastroesophageal junction (GEJ), and must have experienced\n             disease progression during or after first-line therapy for their diseaseXx_NEWLINE_xXHistologically or cytologically confirmed locally advanced or metastatic urothelial carcinoma (UC)Xx_NEWLINE_xXNo prior systemic therapy for inoperable locally advanced or metastatic UCXx_NEWLINE_xXHistologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with EGFR activating mutation (excluding exon 20 insertion); measurable disease per RECIST 1.1Xx_NEWLINE_xXHistologically or cytologically documented unresectable, locally advanced or metastatic breast cancer or gastric cancer refractory to standard therapy.Xx_NEWLINE_xXSubjects must have metastatic or unresectable locally advanced malignant solid tumor.Xx_NEWLINE_xXPatients with advanced malignant solid tumorsXx_NEWLINE_xXDiagnosis of NSCLC with locally advanced or metastatic diseaseXx_NEWLINE_xXHave evidence of persistent, recurrent, or progressive disease for which there is no known or established treatment available with curative intent, after at least one course of systemic therapy for locally advanced or metastatic disease , including chemotherapy, targeted therapy (small molecule or antibody based), or hormonal therapyXx_NEWLINE_xXAge = or > 18 years Histological or cytological diagnosis of undifferentiated or poorly differentiated nasopharyngeal carcinoma that is locally advanced or metastatic.Xx_NEWLINE_xXMetastatic or locally advanced diseaseXx_NEWLINE_xXHave advanced or metastatic cancer and be an appropriate candidate for experimental therapy.Xx_NEWLINE_xXPatient has received at least one prior treatment for recurrent, metastatic and /or locally advanced disease and for whom no standard therapy options are anticipated to result in a durable remission.Xx_NEWLINE_xXPatient must have received at least one prior treatment for recurrent, metastatic and/or locally advanced disease and for whom no standard therapy options are anticipated to result in a durable remission.Xx_NEWLINE_xXPatients must have a metastatic or unresectable locally advanced malignant solid tumor, histologically confirmed by the Laboratory of Pathology, National Cancer Institute (NCI); in the case of chordoma, unresectable, locally recurrent, or metastatic tumors are acceptable for enrollment, given that this represents incurable disease; efforts will be made, as much as possible, to enroll patients with tumor types with known increased expression of brachyury (such as lung, breast, ovarian, prostate, colorectal, pancreatic, or chordoma; other tumors may be included as data on the level of brachyury in those tumors becomes available)Xx_NEWLINE_xXCytologically or histologically confirmed advanced gastric or GEJ adenocarcinoma that is metastatic or locally advanced and unresectable.Xx_NEWLINE_xXMetastatic or locally advanced disease not amenable to curative surgery and/or radiotherapyXx_NEWLINE_xXSubjects with advanced/metastatic Colorectal Cancer(CRC) who have failed or been intolerant to both irinotecan- and oxaliplatin- based regimensXx_NEWLINE_xXSubjects with advanced/metastatic Squamous cell carcinoma of the head and neck (SCCHN) who are without options for curative treatmentXx_NEWLINE_xXDocumented radiographic disease progression following at least one line of therapy in the advanced/metastatic settingXx_NEWLINE_xXLocally advanced or metastatic diseaseXx_NEWLINE_xXPrior systemic therapy for locally advanced or metastatic hepatocellular cancerXx_NEWLINE_xXHistologically confirmed, locally advanced or metastatic HCC.Xx_NEWLINE_xXInoperable metastatic or locally advanced unresectable diseaseXx_NEWLINE_xXHistological documentation of incurable, locally advanced, or metastatic non-squamousXx_NEWLINE_xXLocally advanced or metastatic solid KRAS-mutant tumors, for which standard therapies do not exist, have proven ineffective or intolerable or are considered inappropriateXx_NEWLINE_xXPresence of locally advanced or metastatic disease with at least one measurable lesion.Xx_NEWLINE_xXPatients must have evidence of recurrent, locally advanced, or metastatic disease.Xx_NEWLINE_xXFor expansion cohort only: Subjects with histologically or cytologically proven metastatic breast cancer (with and without AKT1 E17K (G49A) mutation) or subjects with known AKT1 E17K (G49A) mutation in any other advanced solid tumor with at least one line of chemotherapy in the metastatic setting and not amenable to surgery with curative intentXx_NEWLINE_xXPatients with a documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic.Xx_NEWLINE_xXFor docetaxel combination arms: histologically or cytologically documented adenocarcinoma of the breast with locally recurrent or metastatic disease or histologically documented advanced (Stage IV) or recurrent NSCLCXx_NEWLINE_xXReceived no prior chemotherapy for advanced or metastatic disease (Part 2 and Part 2a)Xx_NEWLINE_xXSubjects with histologically confirmed, locally advanced or metastatic, refractory solid tumors who are not candidates for standard therapyXx_NEWLINE_xXPrevious extensive radiotherapy except limited field RT for locally advanced nasal NK PTCL or for pain palliationXx_NEWLINE_xXTreatment with at least two prior systemic therapies for advanced (unresectable locoregional or metastatic) diseaseXx_NEWLINE_xXMetastatic or unresectable locally advanced/recurrent breast cancerXx_NEWLINE_xXLocally advanced basal cell carcinoma lesion that is considered to be inoperable or to have medical contraindications to surgeryXx_NEWLINE_xXPatients must have histologically confirmed breast cancer that is:\r\n* Metastatic; OR\r\n* Incurable and locally advanced, as determined by the treating physicianXx_NEWLINE_xXPatients must have histologically confirmed, radiologically measurable metastatic or locally advanced unresectable colorectal adenocarcinoma that is amenable to image-guided biopsy; disease in previously radiated regions may not be considered measurable unless there has been demonstrated progression in the lesionXx_NEWLINE_xXStage IV disease or inoperable locally advanced disease.Xx_NEWLINE_xXPatients with a documented (histologically- or cytologically-proven) epithelial cell/adenocarcinoma of the pancreas that is relapsed, locally advanced, or metastatic.Xx_NEWLINE_xXSubject with more than 2 prior cytotoxic therapies (not including treatment administered for locally curable disease) for unresectable or metastatic gastroesophageal adenocarcinoma.Xx_NEWLINE_xXKnown advanced malignant hepatic tumorsXx_NEWLINE_xXHistologically or cytologically confirmed: solid malignancy or lymphoma that is metastatic or unresectable, and for which standard curative treatment is no longer effective (Part 1); any type of advanced or refractory solid malignancy (excluding lymphoma) that is metastatic or unresectable and for which standard curative treatment is no longer effective (Part 2); advanced or refractory squamous non-small cell lung cancer (Cohort A, Part 3), advanced or refractory small cell lung cancer (Cohort B, Part 3), advanced or refractory breast cancer (Cohort C, Part 3), any type of advanced or refractory solid malignancy (excluding lymphoma) ([consisting of one of the following: gastric, head and neck, lung adenocarcinoma, urothelial, glioblastoma multiforme (GBM), ovarian or prostate]) (Cohort D, Part 3), advanced or refractory non small cell lung cancer(Cohort E, Part 4), any type of advanced or refractory solid malignancy (consisting of one of the following: Breast, Urothelial, GBM, Ovarian, Head & Neck, Esophageal, Gastric, and Cholangiocarcinoma) (Cohort F, Part 4)Xx_NEWLINE_xXPathologically confirmed solid tumor, locally advanced / metastatic, refractory after standard therapy, or for which no effective curative or surgical treatment options are availableXx_NEWLINE_xXSubjects with advanced or metastatic solid tumors for whom a chemotherapy regimen is considered appropriateXx_NEWLINE_xXPresence of locally advanced or metastatic disease with at least one measurable lesion.Xx_NEWLINE_xXPrior hormonal therapy for locally advanced or metastatic disease is allowed but this must have been discontinued prior to enrollment; no washout period will be requiredXx_NEWLINE_xXHistologically confirmed GIST that is locally advanced or metastaticXx_NEWLINE_xXWomen or men aged =>18 years with histologically documented triple-negative breast cancer (TNBC) or HR+/HER2- adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to resection with curative intentXx_NEWLINE_xXInclusion Criteria:\n\n        To be eligible for participation in the study, patients must meet the following criteria.\n        Patients who are HRG negative do not need to complete screening procedures beyond HRG\n        assessment.\n\n          1. Patients must have histologically or cytologically confirmed ER+ and/or PR+ (with\n             staining of >1% cells) breast cancer.\n\n          2. Patients with confirmed postmenopausal status due to either surgical/natural menopause\n             or ovarian suppression.\n\n          3. Patients must be HER2 negative.\n\n          4. Patient must have at least one lesion amenable to either core needle biopsy or fine\n             needle aspiration.\n\n          5. Patient must have a positive in-situ hybridization (ISH) test for heregulin, as\n             determined by centralized testing of unstained tumor tissue.\n\n          6. Patients that have progressed following at least one but no more than two prior\n             systemic therapies in the locally advanced or metastatic disease setting.\n\n          7. Patients with documented progression of locally advanced or metastatic disease as\n             defined by RECISTv1.1 (Exception: patients with bone-only metastatic disease are\n             eligible if they have at least 2 lytic lesions visible on a CT or MRI and have\n             documented disease progression on prior therapy based on the appearance of new\n             lesions).\n\n          8. Patients with bone-only lesions who have received radiation to those lesions must have\n             documented progression following radiation therapy.\n\n          9. ECOG Performance Score (PS) of 0 or 1.\n\n         10. Patients with adequate bone marrow reserves.\n\n         11. Adequate hepatic function.\n\n         12. Adequate renal function.\n\n         13. Patient has recovered from clinically significant effects of any prior, surgery,\n             radiosurgery, or other antineoplastic therapy.\n\n         14. Patients who have experienced a venous thromboembolic event within 60 days of signing\n             the main consent form should have been treated with anti-coagulants for at least 7\n             days prior to beginning treatment and for the duration of treatment on this study.\n\n        Exclusion Criteria:\n\n        Patients must meet all the inclusion criteria listed above and none of the following\n        exclusion criteria.\n\n          1. Prior treatment with an anti-ErbB3 antibody.\n\n          2. Prior treatment with a chemotherapy in the locally advanced or metastatic disease\n             setting.\n\n          3. Patients cannot have received prior treatment with fulvestrant or other SERDs in the\n             locally advanced or metastatic setting.\n\n          4. Uncontrolled CNS disease or presence of leptomeningeal disease.\n\n          5. Inflammatory breast cancer.\n\n          6. History of another active malignancy that required systemic therapy in the last 2\n             years. Patients with prior history of in-situ cancer, basal, or squamous cell skin\n             cancer are eligible.\n\n          7. Patients with an active infection, or unexplained fever > 38.5 C during screening\n             visits or on the first scheduled day of dosing, which in the investigator's opinion\n             might compromise the patients participation in the trial or affect the study outcome.\n             At the discretion of the investigator, patients with tumor fever may be enrolled.\n\n          8. Known hypersensitivity to any of the components of seribantumab, fulvestrant, or who\n             have had hypersensitivity reactions to fully human monoclonal antibodies.\n\n          9. NYHA Class III or IV congestive heart failure.\n\n         10. Patients with a significant history of cardiac disease (i.e. uncontrolled blood\n             pressure, unstable angina, myocardial infarction within 1 year or ventricular\n             arrhythmias requiring medication) are also excluded.\n\n         11. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; or active\n             human immunodeficiency virus (HIV) infection, active hepatitis B infection or active\n             hepatitis C infection.Xx_NEWLINE_xXLocally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.Xx_NEWLINE_xXPhase 1: Subjects with advanced or metastatic solid tumors.Xx_NEWLINE_xXPhase 2: Subjects with advanced or metastatic urothelial carcinoma or RCC.Xx_NEWLINE_xXBreast cancer that is locally advanced or metastaticXx_NEWLINE_xXMore than 1 prior chemotherapy given for locally advanced or metastatic diseaseXx_NEWLINE_xXDose Escalation Phase: Patients with advanced or metastatic solid tumors for which no standard therapy is available. For Schedule 6 only: patients with colorectal cancer with liver metastasis. Dose Expansion Phase: Previously treated, metastatic or advanced recurrent malignancy with 1 of the following diagnoses, which has been confirmed histologically or cytologically:Xx_NEWLINE_xXPatients with confirmed HER-2 positive, metastatic or non-operable locally advanced breast or gastric cancerXx_NEWLINE_xXMeasurable metastatic or locally advanced refractory/recurrent malignancies that are HPV-16 or HPV-18 HPV positive by in situ hybridization (ISH) or polymerase chain reaction (PCR) or any cancer from the uterine cervixXx_NEWLINE_xXPrior treatment with an EGFR inhibitor is allowed if it was administered as part of definitive therapy for locally advanced disease and completed >/=1 year before study enrollmentXx_NEWLINE_xXHistologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally advanced disease not amenable to curative resectionXx_NEWLINE_xXPrevious systemic non-hormonal anti-cancer therapy in the metastatic or locally advanced breast cancer settingXx_NEWLINE_xXHistologically or cytologically documented, locally advanced or metastatic solid tumors or lymphoma for which standard therapy either does not exist or has proven ineffective or intolerableXx_NEWLINE_xXMore than two regimens of cytotoxic chemotherapy for the treatment of locally advanced or metastatic cancerXx_NEWLINE_xXPostmenopausal women with HER2-, HR+ locally advanced or metastatic breast cancerXx_NEWLINE_xXPrevious chemotherapy for locally advanced or metastatic breast cancerXx_NEWLINE_xXPatients with advanced cutaneous or subcutaneous in-transit or metastatic melanomaXx_NEWLINE_xXCytological or histological confirmed diagnosis of hepatocellular carcinoma that is locally advanced or metastatic and is not amenable to treatment with surgery or to orthotopic liver transplant (Phase II)Xx_NEWLINE_xXHistologically documented, incurable, locally advanced or metastatic disease for which no standard therapy exists, consisting of one of the following: Unresectable pancreatic ductal adenocarcinoma or platinum-resistant ovarian cancerXx_NEWLINE_xXlocally advanced or metastatic solid tumors with the exception of primary brain tumor, and have failed or are not eligible for standard of care therapy.Xx_NEWLINE_xXHistologic documentation of incurable, locally advanced or metastatic disease that has failed prior chemotherapy and for which no standard therapy exists, including the following: non-squamous NSCLC or non-mucinous and platinum-resistant ovarian cancerXx_NEWLINE_xXProgressive disease within three months of completion of curatively intended treatment for locoregionally advanced or metastatic HNSCCXx_NEWLINE_xXHistologically proven, unresectable, locally advanced or metastatic liposarcoma (dedifferentiated, myxoid round cell, or pleomorphic) or leiomyosarcoma. Participants must have a pathology report indicating the diagnosis of liposarcoma or leiomyosarcoma that has been reviewed by the sponsor before randomization may occurXx_NEWLINE_xXDocumented evidence of advanced (locally recurrent, locally advanced and/or metastatic) adipocytic (restricted to subtypes listed in Inclusion 1) or leiomyosarcoma, incurable by surgery and/or radiotherapy.Xx_NEWLINE_xXPathologically confirmed recurrent or metastatic advanced solid tumor, for which there is no curative-intent treatment option; pathology confirmation must be performed at Memorial Sloan-Kettering Cancer Center (MSKCC)Xx_NEWLINE_xXPart A- Diagnosed with advanced and/or metastatic cancer during dose escalationXx_NEWLINE_xXUnresectable locally advanced or metastatic HCC;Xx_NEWLINE_xXHave histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic. The patient must be, in the judgment of the investigator, an appropriate candidate for experimental therapy.Xx_NEWLINE_xXMetastatic or locally advanced unresectable RCC. NOTE: Prior nephrectomy is not mandatory.Xx_NEWLINE_xXConfirmed adenocarcinoma of the breast with locally recurrent or metastatic diseaseXx_NEWLINE_xXHave newly diagnosed localized or locally advanced (T1N1-3M0 or T2-4NanyM0), potentially resectable disease without any prior systemic chemotherapyXx_NEWLINE_xXHistologically or cytologically confirmed, locally advanced or metastatic squamous NSCLCXx_NEWLINE_xXSubject has histologically or cytologically confirmed metastatic or locally advanced, unresectable solid tumors harboring EGFR mutations.Xx_NEWLINE_xXHistologically documented diagnosis of locally advanced or metastatic squamous cell carcinoma (SCC) of the head and neck no longer amenable to curative surgical resection or radiation therapyXx_NEWLINE_xXPhase II: Patients that previously received systemic chemotherapy for metastatic or advanced pancreatic adenocarcinoma are not eligibleXx_NEWLINE_xXPatients must have progressed during or after at least one previous systemic, anti-cancer treatment for locally advanced or metastatic NSCLC.Xx_NEWLINE_xXPatients must have “advanced disease”; usually, this will mean metastatic disease; this may also be multiply recurrent disease or locally advanced disease; locally advanced disease is defined for this study as disease where a mutilating surgery is required and the patient is more likely than not to die of their disease despite an aggressive operation; patients with metastatic disease that has been resected or radiated are allowed to participate; Response Evaluation Criteria in Solid Tumors (RECIST) evaluable disease is not necessary for participationXx_NEWLINE_xXPATIENT: Diagnosed with advanced non-small cell lung carcinoma (NSCLC) being treated with non-curative intent, and informed of advanced disease within the prior eight weeksXx_NEWLINE_xXParticipants with histologically or cytologically confirmed advanced metastatic or unresectable colorectal cancer (CRC) that is relapsed, refractory, or progressive following at least 2 prior systemic regimens in the metastatic setting.Xx_NEWLINE_xXLocally advanced, recurrent, or metastatic, PIK3CA mutant, incurable solid tumor malignancy, including breast cancer Stages I and II, Arm B:Xx_NEWLINE_xXPostmenopausal female participants with histologically documented locally advanced or metastatic PIK3CA-mutant HR+/HER2- breast cancerXx_NEWLINE_xXPostmenopausal female participants with locally advanced or metastatic PIK3CA-mutant HR+/HER2? breast cancer Stages I and II:Xx_NEWLINE_xXKey Inclusion Criteria\n\n        All Study Parts:\n\n          -  Diagnosis of cancer that has been histologically or cytologically confirmed\n\n          -  Eastern Cooperative Oncology Group Performance Status of 0 or 1\n\n        Part A (1 of the following):\n\n          -  Ovarian cancer, triple-negative breast cancer, head and neck squamous cell cancer,\n             bladder cancer, metastatic colorectal cancer, pancreatic ductal adenocarcinoma, or\n             gastric cancer that is measurable or evaluable, nonmeasurable as defined by RECIST\n             v1.1 and meets 1 of the following criteria:\n\n               -  is refractory to standard of care\n\n               -  no standard therapy available\n\n               -  patient refuses standard therapy\n\n          -  Advanced, unresectable, or metastatic melanoma with or without prior treatment and\n             measurable or evaluable, nonmeasurable disease as defined by RECIST v1.1\n\n          -  Advanced/metastatic PD-L1-positive NSCLC (defined as a tumor proportion score [TPS] ?\n             50%) with measurable or evaluable, non-measurable disease as defined by RECIST v1.1 (1\n             of the following):\n\n               -  1) No prior systemic chemotherapy if tumor does not have EGFR or ALK genomic\n                  aberrations\n\n               -  2) Disease progression on or after platinum-containing chemotherapy;\n\n               -  3) If tumor has EGFR or ALK genomic aberrations, disease progression on an\n                  FDA-approved therapy for EGFR or ALK genomic tumor aberrations\n\n        Phase 2 (1 of the following):\n\n          -  Advanced/metastatic solid tumor with PD as defined by RECIST 1.1 or irRC on an\n             anti-PD-1- or anti-PD-L1-containing regimen as their most recent prior therapy\n\n          -  Advanced/metastatic epithelial ovarian cancer, peritoneal cancer or tubal cancer with\n             measurable disease as defined by RECIST 1.1, that had progressed within 6 months of\n             completing ? 4 cycles of platinum-based therapy\n\n          -  Advanced/metastatic PDA that is locally advanced, unresectable or metastatic with\n             measurable disease as defined by RECIST v1.1 in patients who have received at least\n             one prior line of systemic therapy for their disease\n\n        Key Exclusion Criteria\n\n          1. Prior treatment as follows:\n\n               -  Part A: an immune CPI (e.g., PD-1, PD-L1, or cytotoxic T-lymphocyte antigen 4\n                  [CTLA-4] inhibitor).\n\n             NOTE: For patients with melanoma, prior treatment with ipilimumab is allowed if it was\n             administered as adjuvant therapy and treatment was completed at least 3 months prior\n             to enrollment.\n\n               -  Phase 2:\n\n                    -  A CSF-1R inhibitor or CSF-1 (or MCSF) inhibitor.\n\n                    -  prOVCA and PDA patients only: an immune CPI (e.g., PD-1, PD-L1, or CTLA-4\n                       inhibitor)\n\n          2. Symptomatic brain metastasis at screening\n\n          3. Active autoimmune disease, documented history of autoimmune syndrome or disease, or a\n             chronic medical condition that requires chronic steroid therapy or immunosuppressive\n             medication\n\n          4. History of pneumonitis or interstitial lung disease\n\n          5. Severe, acute, or chronic medical or psychiatric condition or laboratory abnormality\n             that may increase the risk associated with study participation or study drug\n             administration or that may interfere with the interpretation of study results and, in\n             the judgment of the Investigator, would make the patient an inappropriate candidate\n             for the study\n\n          6. Ocular melanomaXx_NEWLINE_xXPhase 1-Diagnosis of advanced or metastatic solid tumor; Phase 2-Diagnosis of NSCLCXx_NEWLINE_xXPatients with metastatic and/or advanced solid tumors or lymphomas not amenable to curative treatment by surgery.Xx_NEWLINE_xXHistologically documented advanced or metastatic solid tumors or lymphomasXx_NEWLINE_xXPatients must have at least 1 standard treatment regimen in the advanced, recurrent or metastatic settingXx_NEWLINE_xXDiagnosis of histologically-confirmed esophageal, gastric, pancreatic, or colorectal that is metastatic or locally-advanced (unresectable)Xx_NEWLINE_xXPatient is at least 3 weeks post-diagnosis of an incurable (locally advanced or metastatic) solid malignancyXx_NEWLINE_xXAdvanced, incurable cancerXx_NEWLINE_xXPATIENTS: Diagnosis of advanced cancer (defined as locally advanced, metastatic recurrent, or incurable disease)Xx_NEWLINE_xXPatients with sarcoma which is locally advanced, at high risk for relapse or metastatic for whom treatment with doxorubicin plus ifosfamide (AI) or AI and vincristine (VAI) is indicatedXx_NEWLINE_xXDefinition of advanced cancer includes those patients who have metastatic or refractory disease according to their treating oncologistXx_NEWLINE_xXHave borderline resectable or unresectable locally advanced disease or metastatic diseaseXx_NEWLINE_xXIntraoperative evidence of metastatic or locally-unresectable diseaseXx_NEWLINE_xXAdvanced rheumatoid arthritisXx_NEWLINE_xXPresence of residual or recurrent cancer (locally or metastatic)Xx_NEWLINE_xXDiagnosis of locally advanced, recurrent, or metastatic disease.Xx_NEWLINE_xXPatients with advanced cancer (locally advanced, metastatic, recurrent and/or incurable cancer)Xx_NEWLINE_xXPatients with documented advanced cardiac or renal diseaseXx_NEWLINE_xXPatients with diagnosis of advanced cancer, including recurrent, locally advanced, or metastatic cancerXx_NEWLINE_xXPatients with locally advanced surgically unresectable PDACXx_NEWLINE_xXParticipants with advanced or metastatic and/or unresectable HCCXx_NEWLINE_xXHistologically or cytologically confirmed locally advanced or metastatic adenocarcinoma of the stomach or GEJ in participants who have not received prior systemic therapy for metastatic diseaseXx_NEWLINE_xXPatients with only locally advanced diseaseXx_NEWLINE_xXSubjects must have histologic documentation of advanced recurrent or metastatic cancer.Xx_NEWLINE_xXSubjects must be at the recurrent/metastatic setting, with selected advanced solid tumors.Xx_NEWLINE_xXAdvanced unresectable or metastatic diseaseXx_NEWLINE_xXHistologically and/or cytologically proven unresectable locally advanced or metastatic tumors that express B7-H3 on the membrane or vasculature. The requirement for previous systemic therapy may be waived if a person was intolerant of standard front-line therapyXx_NEWLINE_xXHistologically documented advanced or metastatic solid tumors.Xx_NEWLINE_xXPathologically confirmed locally advanced or metastatic disease per the treating institution's standard of care of the following tumor types: \r\n* Subjects with histologically confirmed locally advanced/unresectable or metastatic melanoma who meet all of the following criteria: \r\n** Subjects have received any number of prior lines of therapy or may be treatment naive \r\n** If the subject has been treated with a prior line of therapy, they must have had disease progression or be refractory to treatment OR \r\n* Subjects with histologically or cytologically confirmed locally advanced/unresectable or metastatic urothelial carcinoma (including mixed histologies of urothelial carcinoma with elements of other subtypes) of the renal pelvis, ureter, bladder or urethra (referred to broadly in this protocol as “bladder cancer”) who meet the following criteria: \r\n** Subjects must have disease progression or refractory disease after their prior line of therapy; subjects must have had at least 1 platinum based chemotherapy regimen for the treatment of metastatic or locally advanced unresectable disease; subjects may have received any number of prior lines of therapy OR \r\n** Subjects with disease recurrence within 1 year of a platinum based neoadjuvant or adjuvant therapy for bladder cancer OR \r\n** The subject actively refuses chemotherapy for the treatment of metastatic or locally advanced disease considered as standard treatment for this disease stage (i.e. a patient who has relapsed > 1 year after treatment with neoadjuvant or adjuvant chemotherapy), despite being informed by the investigator about the treatment options; the subject’s refusal must be documentedXx_NEWLINE_xXUnresectable, locally advanced or metastatic disease; diagnosed within 6 weeks prior to screeningXx_NEWLINE_xXPrior treatment of pancreatic cancer in the metastatic setting (or locally advanced setting) with surgery (placement of stent is allowed), radiotherapy, chemotherapy or investigational therapyXx_NEWLINE_xXStage IV, locally advanced or metastatic urothelial bladder cancer or transitional cell carcinoma arising in another location of the urinary tract, including urethra, ureter, and renal pelvisXx_NEWLINE_xXMetastatic or locally recurrent unresectable breast cancerXx_NEWLINE_xXDiagnosis of advanced cancer (defined as locally advanced, metastatic, recurrent, or incurable disease)Xx_NEWLINE_xXLocally recurrent or metastatic diseaseXx_NEWLINE_xXPatients who have been diagnosed with locally advanced unresectable NSCLC undergoing definite chemo-radiation with curative intentXx_NEWLINE_xXLocally advanced breast cancer patients treated with surgery and adjuvant radiationXx_NEWLINE_xXNo locally advanced or metastatic cancer requiring systemic therapy within 5 years prior to registration; no secondary primary lung cancer diagnosed concurrently or within 2 year prior to registrationXx_NEWLINE_xXPatients with active, progressive or advanced disease based on diagnosisXx_NEWLINE_xXCurrent or prior advanced adenomasXx_NEWLINE_xXHave histologically confirmed solid malignancy including but not limited to: pancreas, lung, stomach, colon, rectum, bladder, breast, ovary, renal or lymphoma (hematologic), with locally advanced or metastatic diseaseXx_NEWLINE_xXHistologically or cytologically documented metastatic or unresectable, locally advanced or metastatic NSCLC, with one or more activating EGFR mutation (eg, G719X, exon 19 deletion, L858R, L861Q) and absence of exon 20 insertionXx_NEWLINE_xXPhase Ib dose escalation only: Any number of prior lines of endocrine therapy is allowed with the exception of cytotoxic therapy which is limited to one prior line administered in the advanced (metastatic or locally advanced) setting.Xx_NEWLINE_xXNo prior systemic treatment in the advanced (metastatic or locally advanced) setting with the exception of treatment with letrozole for a maximum of one month prior to starting study treatment.Xx_NEWLINE_xXLocally advanced disease which is unresectable, or resectable but suitable for an organ sparing approachXx_NEWLINE_xXAdult women > 18 years of age with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapyXx_NEWLINE_xXPatients presenting with locally advanced disease in the breast (cT4) and/or in the nodes (cN2/N3) as assessed by clinical exam and imagingXx_NEWLINE_xXPatients with histologically confirmed pancreatic adenocarcinoma (borderline resectable or locally advanced disease at presentation) are eligible for the studyXx_NEWLINE_xXHistologically confirmed, locally-advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) or other malignancies known to express CA19-9 positive malignanciesXx_NEWLINE_xXPatients who have known metastatic disease or other locally advanced disease in the thoracic or cervical regionsXx_NEWLINE_xXAdvanced periodontal disease (gum disease)Xx_NEWLINE_xXPatient with advanced skin cancersXx_NEWLINE_xXHormone therapy for locally advanced disease (except patients on 5-alpha reductase inhibitors to reduce the size of the prostrate)Xx_NEWLINE_xXHas locally advanced or metastatic NSCLC, not amenable to curative surgery or radiationXx_NEWLINE_xXSubject has histologically or cytologically documented diagnosis of pancreatic adenocarcinoma with metastatic disease. Locally advanced subjects are not eligible.Xx_NEWLINE_xXPatients initially diagnosed with locally advanced pancreatic cancer who have undergone chemotherapy then resection and were with no evidence of disease are eligible if metastatic relapse of disease has occurred and if the last dose of chemotherapy was more than 4 months before the data of study entry.Xx_NEWLINE_xXDose Escalation Segment: histologically and / or cytological confirmed locally advanced, recurrent or relapsed, or metastatic incurable solid malignancy with no limit on the number of prior lines of standard therapy.Xx_NEWLINE_xXLocally advanced or metastatic, unresectable sarcoma that has progressed after treatment with 150 mg/m2 or less of doxorubicin or anthracycline equivalentXx_NEWLINE_xXINCLUSION:\n\n        All Patients\n\n          1. Male or female aged ?18 years.\n\n          2. ECOG PS score of 0-1.\n\n          3. Adequate organ function.\n\n          4. Ability to understand and willingness to sign informed consent form prior to\n             initiation of study procedures.\n\n          5. Measurable disease per RECIST, OR for patients with a primary diagnosis of castration\n             resistant prostate cancer, progressive disease (PD) by prostate surface antigen (PSA)\n             or imaging in the setting of medical or surgical castration.\n\n          6. Documented BRCA mutation, with the following exceptions: a) Patient is intended to be\n             enrolled in a Single-patient Cohort; b) Patient has an advanced DNA repair\n             mutation-positive solid tumor and is intended to be enrolled in Expansion Cohort 5.\n\n             Patients in the Dose-escalation Phase:\n\n          7. Locally advanced solid tumor other than a primary central nervous system (CNS) tumor\n             for which the patient has received ?3 prior lines\n\n          8. Confirmed solid tumor in one of the following categories:\n\n               -  BRCA mutation-positive pancreatic cancer for which the patient received up to 1\n                  prior line of cytotoxic chemotherapy in the advanced disease setting.\n\n               -  Advanced BRCA mutation-positive castration-resistant prostate cancer (CRPC) for\n                  which the patient received up to 2 prior lines of cytotoxic chemotherapy in the\n                  advanced disease setting.\n\n               -  Advanced BRCA mutation-positive ovarian cancer for which the patient received up\n                  to 3 prior lines of cytotoxic chemotherapy in the advanced disease setting.\n\n               -  Advanced BRCA mutation-positive triple-negative breast cancer (TNBC) for which\n                  the patient received up to 3 prior lines of cytotoxic chemotherapy in the\n                  advanced disease setting.\n\n               -  Advanced DNA repair mutation-positive solid tumors, including, but not limited to\n                  BRCA and non-BRCA DNA mutations, who have received up to 3 prior lines of\n                  cytotoxic chemotherapy in the advanced disease setting. DNA-repair mutations may\n                  include, but are not limited to ATM, CHEK2, PALB2, and RAD51D. Abnormal\n                  homologous repair deficiency (HRD) tests will also be allowed.\n\n        Note that in both dose escalation and dose expansion portions of the study, prior targeted\n        therapy including prior poly ADP ribose polymerase (PARP) inhibitor therapy, prior\n        immunotherapy, or prior hormonal therapy is permissible. Patients with castration resistant\n        prostate cancer may have received unlimited prior hormonal therapies.\n\n        EXCLUSION:\n\n          1. History of leptomeningeal disease or spinal cord compression.\n\n          2. Underwent major surgery within 4 weeks before first treatment.\n\n          3. Received cancer-directed therapy 14 days (6 weeks for mitomycin C and nitrosoureas)\n             before start of treatment.\n\n          4. Grade 2 or greater peripheral neuropathy at start of treatment.\n\n          5. If female, pregnant or breast-feeding.\n\n          6. Known human immunodeficiency virus (HIV) infection or hepatitis B or C infection\n\n          7. Any primary brain tumor (e.g., astrocytoma, glioblastoma).\n\n          8. Hypersensitivity or history of anaphylactic reaction to any platinum-containing\n             agents.Xx_NEWLINE_xXLocally advanced disease as determined by endoscopic rectal ultrasound (ERUS) or pelvic MRI; endoscopy reports should clearly state both the T and N stageXx_NEWLINE_xXLocally advanced breast cancer, defined as being clinically appropriate for neoadjuvant chemotherapyXx_NEWLINE_xXSubject has been diagnosed with an advanced solid malignancy; advanced solid malignancy is defined as loco regional or systemic metastatic disease of at least 1 cm in diameter; tumor types allowed include: triple negative breast, prostate, colorectal, gastric, ovarian, pancreatic, esophageal, soft tissue sarcoma, and head & neck cancer; subjects with primary or metastatic skin disease only are excluded from participation in this studyXx_NEWLINE_xXPatients with metastatic or locally unresectable PDAC* (resectability is as defined by MSKCC pancreatic surgeon)Xx_NEWLINE_xXDiagnosed with advanced (metastatic or unresectable) sarcomaXx_NEWLINE_xXSubject must have histologic or cytologic confirmation of advanced melanomaXx_NEWLINE_xXHave histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastaticXx_NEWLINE_xXPatients with histologic or cytologic diagnosis of advanced or metastatic solid tumors or lymphomas for which no curative or life-prolonging therapies exist.Xx_NEWLINE_xXAdvanced cancer diagnosis (locally advanced, recurrent or metastatic disease)Xx_NEWLINE_xXPatients with a diagnosis of advanced cancer, including recurrent, locally advanced, or metastatic cancerXx_NEWLINE_xXPatients with the diagnosis of advanced cancer defined as locally advanced, recurrent or metastatic diseaseXx_NEWLINE_xXDiagnosis of advanced cancer, defined as locally advanced, recurrent or metastatic diseaseXx_NEWLINE_xXHormone therapy for locally advanced disease (except patients on 5-alpha reductase inhibitors to reduce the size of the prostate)Xx_NEWLINE_xXLocally advanced or metastatic head and neck cancer.Xx_NEWLINE_xXAdvanced or Metastatic renal cell carcinoma (RCC)Xx_NEWLINE_xXNo more than 3 total prior systemic treatment regimens in the advanced or metastatic settingXx_NEWLINE_xXHistologically or cytologically documented, locally advanced or metastatic solid tumors for which standard therapy either does not exist or has proven ineffective or intolerableXx_NEWLINE_xXLocally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.Xx_NEWLINE_xXPart 1: Subjects with advanced or metastatic solid tumors.Xx_NEWLINE_xXParticipants must have metastatic or locally advanced incurable anal cancer that has been histologically confirmed; patients with locally advanced anal cancer must have had cancer recurrence after chemoradiation and must be unresectableXx_NEWLINE_xXNo prior chemotherapy for inoperable locally advanced or mUCXx_NEWLINE_xXLocally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intentXx_NEWLINE_xXPart 1: Subjects with advanced or metastatic solid tumorsXx_NEWLINE_xXAdvanced Solid Malignancies: Histologically documented metastatic or locally advanced, incurable solid malignancy (Parts A and B); histologically documented metastatic or locally advanced, incurable solid malignancy for which gemcitabine is clinically appropriate (e.g., non-small cell lung, breast, ovarian, pancreatic, and renal cancer); histologically documented metastatic or locally advanced, incurable solid malignancy for which pembrolizumab (Part D) or nivolumab (Part E) is approved. NOTE: Parts D and E only: Subject has either (1) received treatment with pembrolizumab or nivolumab for ?4 months with a best response of stable disease and plans to continue treatment with either pembrolizumab or nivolumab in accordance with package insert; or (2) is not currently taking, but is eligible for treatment with, pembrolizumab or nivolumab in accordance with the approved indications for each as referenced in the package insert.Xx_NEWLINE_xX