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+Part 1: Patient with any advanced or metastatic solid tumor
+Part 2A: Patient with any advanced or metastatic solid tumor
+Patients must have histologically confirmed epithelioid hemangioendothelioma which is metastatic or locally advanced (unresectable)
+Histologically- or cytologically-confirmed diagnosis of locally advanced or metastatic solid tumor that harbors an NTRK1/2/3, ROS1, or ALK gene rearrangement
+Must have histologically confirmed advanced CRC that is metastatic.
+The patient has metastatic disease or locally recurrent, unresectable disease
+Metastatic disease or locally advanced disease that is not resectable.
+No 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 registration
+Patients must have histologically or cytologically documented adenocarcinoma of the colon or rectum that is metastatic or locally advanced and unresectable
+Patients 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 Form
+Patients 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 eligible
+Locally advanced/unresectable or metastatic disease
+Re-registration: locally advanced/unresectable or metastatic disease
+Patients 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 permitted
+Locally advanced or metastatic disease; locally advanced disease is defined as disease not amenable to local therapy such as surgery and/or radiation
+No prior immunotherapy for advanced/metastatic MCC
+No prior chemotherapy or targeted systemic therapy for inoperable locally advanced or metastatic TNBC
+Chemoradiation 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.
+Locally 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)
+Histologically or cytologically confirmed diagnosis of selected locally advanced or metastatic solid tumors
+Must have failed at least 1 prior treatment regimen for locally advanced or metastatic disease or be intolerant to treatment or refuse standard treatment
+Subjects 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 histologically
+Histological or cytological evidence of confirmed metastatic pancreatic or advanced bladder cancer
+3. 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;
+Locally advanced or metastatic HER2-positive breast cancer that has relapsed or is refractory to established therapies
+Diagnosed with histologically or cytologically confirmed locally advanced/metastatic NSCLC with EGFR mutation
+Histologic 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 biopsy
+In 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 setting
+In 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 disease
+In 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 disease
+Histologic or cytological confirmation of a malignancy that is advanced (metastatic and/or unresectable) with measureable disease per RECIST v1.1
+Disease that is unresectable, locally advanced, or metastatic (not amendable to curative therapy)
+Metastatic 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 study
+Dose 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).
+Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumor that is not amenable for treatment with curative intent as follows:
+Prior chemotherapy or any other investigational agents for the treatment of locally advanced or metastatic pancreatic cancer
+Histologically 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);
+Histologically 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.
+Any 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 chemoradiation
+Participant 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.
+Histologically confirmed locally advanced melanoma (pembrolizumab only), metastatic NSCLC (pembrolizumab only) locally advanced or metastatic urothelial carcinoma (atezolimumab only).
+Have not received prior anti-cancer therapy for advanced or metastatic melanoma
+Histologically or cytologically documented locally advanced or metastatic urothelial carcinoma
+No prior chemotherapy or targeted systemic therapy (including endocrine therapy) for inoperable locally advanced or metastatic TNBC
+Have locally advanced (on TNM staging: T4b and any N, or any T and N2-3) or metastatic transitional cell carcinoma of the urothelium, including of the urinary bladder, urethra, ureter, and/or renal pelvis. The diagnosis must be histologically or cytologically confirmed.
+Advanced 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 required
+Histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumor (including non-Hodgkin Lymphoma) (Stage IV, AJCC v.7) that harbors an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement by protocol specified tests.
+Progressive metastatic or locally advanced or metastatic breast cancer.
+Subject 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.
+RASMUT/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.
+SCCHN: 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.
+Locally advanced unresectable or metastatic disease that has progressed since last treatment.
+Histologically or cytologically confirmed adenocarcinoma of the breast with unresectable locally advanced disease, or metastatic disease and HER2 IHC 1+ or 2+ OR
+Histologically or cytologically confirmed adenocarcinoma of the breast with unresectable locally advanced disease, or metastatic disease and HER2 IHC 3+ or positive for HER2 gene amplification
+Histologically or cytologically confirmed locally advanced or metastatic gastric cancer and HER2 IHC 3+ or positive for HER2 gene amplification OR
+Histological or cytological diagnosis of metastatic cancer or locally advanced cancer that is not amenable to local therapy
+Subject must have locally advanced or metastatic solid tumor with no additional therapy options available that are known to provide clinical benefit per institutional standards;
+Diagnosed with advanced or metastatic malignancy
+Locally advanced, unresectable or metastatic disease
+For 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.
+For 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.
+Patients with confirmed advanced hematological malignancies
+For Part B exclusively (RO6874281 in combination with trastuzumab), participants with metastatic or recurrent or locally advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer, as defined by the College of American Pathologists HER2 testing guidelines, who have progressed on at least two lines of HER2-directed therapies in the metastatic setting and the last therapy prior to going on study has to contain a HER2-directed antibody; baseline left ventricular ejection fraction (LVEF) of >=50% (measured by echocardiography) predose on Cycle 1 Day 1
+All subjects must have previously treated either locally advanced or metastatic renal or urothelial cell carcinoma to be eligible for participation
+Disease site/type with pathologic confirmation of diagnosis at participating cancer site; Note: if recurrence occurred greater than two years after resection, a biopsy to confirm recurrence should be performed and used for confirmation of diagnosis at the participating site\r\n* Phase 1: Advanced, unresectable sarcoma (any subtype, except for patients with pigmented villonodular synovitis for which metastatic disease is required)\r\n* Phase 2: Advanced, unresectable malignant peripheral nerve sheath tumors (MPNSTs)
+Metastatic disease or locally advanced, unresectable disease
+Locally advanced or metastatic NSCLC
+Has histologically or cytologically confirmed metastatic, or unresectable locally advanced, recurrent NSCLC.
+Histologically-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)
+Patient with histological proven metastatic GIST or non-operable locally advanced GIST
+Relapsed, locally-advanced or metastatic colorectal or pancreatic cancer, squamous NSCLC, or SCCHN patients who are not candidates for standard therapy.
+Histologic or cytologic confirmation of an incurable solid malignancy that is advanced (metastatic and/or unresectable), with measurable disease per RECIST v1.1
+Histologic 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 biopsy
+Have histologically or cytologically confirmed locally advanced or metastatic transitional cell carcinoma of the urothelium (renal pelvis, ureter, urinary bladder or urethra)
+Refractory or intolerant to at least one prior standard therapy(ies) for metastatic or locally advanced disease.
+During 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.
+Histologically or cytologically confirmed locally advanced or metastatic Triple Negative Breast Cancer.
+Advanced disease is defined as metastatic disease or locally advanced disease that is not amenable to surgery or radiotherapy with curative intent
+Part 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.
+Patients must have a histologically confirmed metastatic and/or locally advanced sarcoma by the enrolling institution.
+Prior therapy for breast cancer in the advanced/metastatic setting must have included at least:
+Documented evidence of advanced RCC
+Histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ) adenocarcinoma that is metastatic or locally advanced and unresectable
+Cohort 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 spread
+Histologic 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.
+Patients must have locally advanced, metastatic or refractory leiomyosarcoma or dedifferentiated liposarcoma
+histologic or cytologic confirmation of a solid tumor that is advanced (metastatic, recurrent and/or unresectable)
+PROCUREMENT INCLUSION CRITERIA: Any breast cancer patient with metastatic or locally recurrent unresectable disease
+Any breast cancer patient with metastatic or locally recurrent unresectable breast cancer currently progressive, after at least two prior lines of therapy in the advanced setting; patients with HER2+ disease must have failed two or more different anti-HER2 agents
+During dose escalation only, an additional population with unresectable advanced and/or metastatic 2nd line RCC patients is allowed
+Histologically proven, locally advanced unresectable or metastatic solid tumors for whom no approved therapy with demonstrated clinical benefit is available or standard treatment was declined.
+Histologically or cytologically confirmed diagnosis of locally advanced or metastatic ALK-positive NSCLC; at least 1 extracranial measurable target lesion not previously irradiated. CNS metastases allowed if asymptomatic and not currently requiring corticosteroid treatment.
+Participants 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 evaluation
+Patient with advanced or metastatic solid tumor and has disease progression or treatment intolerance after treatment with available therapies
+Patients must have metastatic disease or locally advanced unresectable disease
+Pathologically confirmed diagnosis of breast cancer with radiographic evidence of incurable, unresectable, locally advanced or metastatic disease (LA/MBC)
+Advanced melanoma or PD-L1-positive advanced, relapsed, or refractory solid tumor or lymphoma
+Cohort 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 SETD2
+No prior systemic therapy in the metastatic or advanced setting
+Disease 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 eligible
+Has a diagnosis of locally advanced or metastatic solid tumor
+HER2-expressing cancer as follows: Part 1: Any locally advanced (unresectable) and/or metastatic HER2-expressing (HER2 1+, 2+, or 3+ by IHC) cancer that has progressed after receipt of all therapies known to confer clinical benefit
+HER2-overexpressing (3+ by IHC) or HER2 2+ and FISH positive gastric cancer must have progressed after prior treatment with trastuzumab Part 2: ? Locally advanced (unresectable) and/or metastatic cancer that has progressed after receipt of all therapies know to confer clinical benefit (unless ineligible to receive a specific therapy) as follows:
+Pts 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:
+Have advanced or metastatic cancer (solid tumors) and be an appropriate candidate for experimental therapy.
+Part 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)
+Confirmed diagnosis of borderline resectable or locally advanced pancreatic adenocarcinoma
+Locally advanced unresectable or metastatic stage 4 (i.e. T4 or N3 or M1) penile squamous cell carcinoma (PSCC)
+Patients 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 eligible
+advanced pancreatic cancer
+Patients with advanced or metastatic solid tumors who have disease progression after treatment with available therapies and for whom nab-paclitaxel treatment is appropriate.
+Advanced solid tumors
+Has received at least 1, but no more than 2, prior lines of systemic therapy for locally recurrent and/or metastatic disease.
+The 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).
+Dose escalation:\r\n* Any locally advanced or metastatic solid tumor malignancy with no curative treatment options available
+Patients may have received any number of lines of prior systemic therapy for locally advanced/metastatic disease
+Patients with metastatic (lymph node or distant metastasis, i.e. N+ or M1) or locally advanced unresectable PSCC
+Patients with metastatic (lymph node or distant metastasis, i.e. N+ or M1) or locally advanced unresectable (T4b) TCC
+PHASE IB: Histologically confirmed refractory locally-advanced unresectable or metastatic pancreatic or biliary cancer
+PHASE IB: =< 2 lines of prior systemic therapy for patients with progressive locally-advanced disease
+Stage IIIB or IV NSCLC or relapsed locally advanced or metastatic NSCLC
+Locally advanced disease must not be amenable to resection with curative intent
+Any prior chemotherapy, hormonal, or targeted therapy, for inoperable locally advanced or metastatic triple-negative breast cancer (mTNBC)
+(Part 2 only) Cohort 2: Have histologically or cytologically confirmed diagnosis of nonresectable, recurrent, or metastatic biliary tract carcinoma (intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer, or ampullary carcinoma) and have not received prior systemic anticancer therapy for advanced or metastatic disease.
+(Part 2 only) Cohort 3: Have histologically or cytologically confirmed diagnosis of metastatic or locally advanced TCC of the urinary tract (bladder, urethra, ureter, renal pelvis) (T3b-T4 N0 M0, Tany N1-N3 M0, or Tany Nany M1) and are not candidates for surgery.
+Patients must have locally advanced or metastatic urothelial cancer that is not amenable to surgical treatment
+Patient has only locally advanced disease.
+Patients 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)
+Parts A, A2 & B1: Participants must have pathological evidence of a diagnosis of advanced and/or metastatic cancer and must be, in the judgment of the investigator, an appropriate candidate for experimental therapy
+Patients with advanced and/or metastatic, histologically documented solid tumors.
+Patients 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 tumors
+Advanced myelofibrosis
+Cohort C: advanced or metastatic (stage 4) RCC
+Locally 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)
+Sign of locally advanced disease or metastatic bladder cancer
+Have histologically or cytologically documented locally advanced unresectable or metastatic/recurrent urothelial carcinoma (including renal pelvis, ureters, urinary bladder, and urethra);
+For Cohort B: No prior chemotherapy for inoperable locally advanced or metastatic or recurrent UCa and ineligible (\unfit\) for cisplatin-based chemotherapy;
+Documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic; patients with documented lymphomas.
+Locally advanced/unresectable or metastatic disease.
+Patients 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 disease
+Have histologically or cytologically-documented diagnosis of advanced (metastatic and/or unresectable) thymic carcinoma, for which no curative treatment (including surgery, radiation, or other) is available
+Histologically 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)
+Locally advanced or metastatic BC that has relapsed or is refractory to established therapies HER2-Expressing Gastric/Gastroesophageal (GEJ) Cancer-Specific Inclusion Criteria
+Adenocarcinoma of the stomach or GEJ with inoperable locally advanced or recurrent and/or metastatic disease, not amenable to curative therapy
+Diagnosis of advanced or metastatic cancer not amenable to curative therapy
+Histologic 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 investigator
+Subjects 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+
+For 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)
+Diagnosed with (a) locally advanced or metastatic (stage III-IV) breast cancer or (b) advanced prostate cancer
+Parts B of the study will include patients with histological or cytological confirmation diagnosis of locally advanced or metastatic Stage IV NSCLC.
+Part 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).
+Histologically confirmed metastatic or unresectable locally advanced non-squamous NSCLC with documented EGFR mutation-positive disease
+Subjects must have a histologically confirmed metastatic and/or locally advanced sarcoma
+One 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 cohort
+Has a pathologically documented unresectable advanced NSCLC disease not amenable to curative therapy
+Histologic or cytologic confirmation of a solid tumor that is advanced (metastatic, recurrent and/or unresectable) with measurable disease per RECIST v1.1
+Have histologically confirmed, locally advanced unresectable or metastatic (stage IV) colorectal adenocarcinoma
+Patients 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 confirmed
+Histologically confirmed, unresectable advanced solid malignancy with documented disease progression after at least 1 prior systemic therapy
+Histologically confirmed locally advanced and unresectable or metastatic melanoma
+Histologically confirmed diagnosis of metastatic or locally advanced unresectable tumors
+More than 1 line of prior chemotherapy in the treatment of metastatic or locally advanced/recurrent disease.
+Histologically confirmed non-squamous NSCLC, with incurable advanced or metastatic disease
+Patients 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 histology
+Histologically confirmed triple negative breast cancer(TNBC) that is either locally recurrent, inoperable and cannot be treated with curative intent or is metastatic
+Have not received prior chemotherapy or targeted systemic therapy for their locally advanced inoperable or metastatic recurrence. Prior radiation therapy for recurrent disease is permitted
+Participant must have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic.
+Histologically 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)
+Patients with incurable, advanced or metastatic disease refractory to at least one previous line of therapy
+Regimen A only (monotherapy): Subjects with advanced metastatic solid tumors
+Regimen B only (combination with trastuzumab): Subjects with advanced metastatic HER2+ solid tumors
+Regimen C only (combination with cetuximab): Subjects with advanced metastatic EGFR+ solid tumors
+Biopsy proven locally advanced or metastatic prostate cancer.
+Documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic; patients with documented lymphomas.
+Locally advanced or metastatic solid tumors that have exhausted standard of care therapy
+Histologically- or cytologically- confirmed locally advanced or metastatic nonfunctional well differentiated neuroendocrine tumor (WDNET)
+Patients 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.
+Histological 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 disease
+Female patients with histologically-confirmed, unresectable locally advanced or metastatic breast cancer;
+Patients 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;
+Locally advanced, unresectable disease, as defined by NCCN criteria
+Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation.
+Advanced solid tumors
+Stage IV or locally advanced unresectable cancers for which no alternative therapies with proven survival advantage are available
+Patients 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 component
+Has 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 measurable
+Patients must have histologically or cytologically confirmed, inoperable or unresectable locally advanced, or metastatic NSCLC
+Histologically or cytologically confirmed metastatic or unresectable locally advanced, non-squamous, NSCLC
+Histologically 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)
+Patients must have histologically confirmed breast cancer that is metastatic or locally advanced and unresectable
+Stage IV disease or locally advanced/unresectable tumors
+Locally advanced and unresectable or metastatic TNBC or triple negative inflammatory breast cancer.
+Subjects must have histological or cytological documentation of locally advanced, recurrent, or metastatic renal cell carcinoma
+Locally advanced/unresectable disease as determined by site attending urologic oncologist or metastatic disease
+Patients must have histologically or cytologically confirmed invasive breast cancer, which is recurrent, locally advanced, unresectable or metastatic
+Locally 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)
+Advanced or metastatic RCC
+No more than three total prior systemic treatment regimens in the advanced or metastatic RCC setting
+Previously treated, pathologically confirmed, locally advanced or metastatic solid tumors with measurable disease;
+Must 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 eligible
+Patients 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.
+Patient must have pathologically confirmed, locally advanced or metastatic pancreatic ductal adenocarcinoma (PDA) deemed surgically unresectable by a surgeon with expertise in pancreatic cancer
+Evidence of locally advanced or metastatic disease;
+Stage III unresectable locally advanced pancreatic carcinoma
+Diagnosed with advanced (metastatic or unresectable) leiomyosarcoma or liposarcoma
+Pathologically 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 disease
+Subjects must have a histologically confirmed metastatic and/or locally advanced sarcoma
+Subjects 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=12
+PRE-SCREENING: Patients with advanced metastatic pancreatic cancer who have measurable disease
+PRE-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)
+FULL 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)
+Prior exposure to a taxane (paclitaxel or docetaxel)-based regimen in localized or advanced/metastatic setting.
+Locally advanced disease that is not resectable or metastatic disease.
+Unresectable advanced or metastatic RCC to include both clear cell and non-clear histologies
+Advanced Gastric Cancer
+Patients 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 bevacizumab
+Patients 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)
+Locally advanced unresectable or metastatic disease with no standard curative therapy available
+Patients with histologically confirmed locally advanced or metastatic solid carcinomas in Arm 1
+Patients with histologically confirmed locally advanced or metastatic colon cancer in Arm 2
+Patients with histologically confirmed locally advanced or metastatic cholangiocarcinomas in Arm 3
+Patients with histologically confirmed locally advanced or metastatic colon, gastric, ovarian, bladder cancers, as well as cholangiocarcinomas or hepatomas in Arm 4
+Prior 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 enrollment
+Patients must have advanced or metastatic NSCLC
+patients with a histologically confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours (any type).
+patients with a histologically confirmed diagnosis of select advanced, unresectable, and/or metastatic solid tumours with specific histology/tumour types and/or specific genetic profiles
+Male or female advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.
+No more than one prior line of non-gemcitabine/nab-paclitaxel containing systemic therapy for metastatic/locally advanced pancreatic cancer
+More 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 regimen
+Histologic, cytologic, or radiologically evidence of locally advanced, residual, or recurrent solid malignancy of the abdomen or pelvis requiring surgical resection
+Patients must have pathologically confirmed advanced/metastatic cancer prior to enrollment.
+Histologic proof of metastatic or locally advanced, unresectable breast cancer
+Metastatic and/or locally advanced or locally recurrent disease that is not surgically resectable
+Patients must have advanced disease that is not amenable to transplant or resection
+Prior therapy\r\n* Arm A: Rebastinib plus paclitaxel: up to two prior non-taxane chemotherapy regimens for metastatic or incurable locally advanced disease permitted (no prior paclitaxel or eribulin); patients with estrogen receptor (ER)-positive disease are required to have relapse or progression on at least one line of endocrine therapy\r\n* Arm B: Rebastinib plus eribulin: up to three prior chemotherapy regimens for metastatic or incurable locally advanced disease permitted (no prior eribulin, but prior paclitaxel allowed): patients with ER-positive disease are required to have relapse or progression on at least one line of endocrine therapy
+Histologically 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).
+Patients with borderline resectable, locally advanced or metastatic disease
+Stage IV or locally advanced histologically confirmed solid tumors for which no alternative therapies with proven survival advantage are available
+Histologically 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 mutations
+Histologically 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 intent
+Pancreatic 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.
+Histologically confirmed, locally-advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) or other CA19-9 positive malignancies
+Patients with histologically proven, surgically unresectable, locally advanced pancreatic adenocarcinoma (at diagnosis) or with mixed cell type with predominant histology of adenocarcinoma (by NCCN guidelines)
+Unresectable or metastatic breast cancer; locally recurrent disease must not be amenable to any local treatment with curative intent; metastatic disease must be demonstrated either radiographically or histologically
+Patients 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 eligible
+Histologically documented non-keratinizing locally advanced recurrent or metastatic NPC.
+Prior chemotherapy for advanced or metastatic disease
+Histologically and radiologically confirmed advanced metastatic CCRCC in patients who have had at least one prior systemic therapy, which can include axitinib
+Histologic 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 eligible
+To be eligible for Cohorts 1-4, patients must have failed one or two prior lines of systemic therapy for advanced/metastatic disease
+To be eligible for Cohort 6, patients must have failed one prior line of systemic therapy for advanced/metastatic disease
+To be eligible for Cohort 5, patients must not have received any systemic therapy for advanced/metastatic disease
+Histologically or cytologically proven diagnosis of breast cancer with evidence of metastatic or locally advanced disease, not amenable to resection or radiation therapy with curative intent
+Metastatic or unresectable locally advanced
+For 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 therapy
+Patients 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)
+Patients in Part B must have histologically or cytologically-confirmed, locally-advanced, or metastatic solid malignancy within the disease indications of Part A
+Prior systemic therapy directed at advanced or metastatic RCC
+Muscle-invasive, locally advanced nonresectable, or metastatic urothelial carcinoma (i.e., T2, T3, T4, and / or stage IV)
+That 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)
+Received >2 prior systemic anti-cancer drug regimen for locally advanced disease
+Non-hepatocellular carcinoma subjects must have received at least 1 prior standard of care systemic anti-cancer therapy for their locally advanced or metastatic disease.
+ARM A COHORT 1: Patients must have advanced pancreatic adenocarcinoma (unresectable or metastatic)
+ARM C COHORT 4: Patients must have a histologically or cytologically proven diagnosis of advanced (unresectable or metastatic) gallbladder cancer or cholangiocarcinoma and be candidates for first line therapy with gemcitabine and cisplatin
+Histologically or cytologically confirmed locally advanced, inoperable, or metastatic tumors: • Carboplatin Plus Paclitaxel Arm:
+Subjects 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 enrolled
+Subjects 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 enrolled
+Subjects 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 enrolled
+Subjects 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 enrolled
+Have locally advanced or metastatic urothelial cancer that is not amenable to curative surgical treatment\r\n* Have histologically or cytologically confirmed urothelial tract carcinoma
+Patients must have histologic or cytologic diagnosis of advanced/metastatic NSCLC. For those with mixed histology, there must be a predominant histology.
+Cytologic 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 eligible
+Metastatic or locally advanced breast cancer for which endocrine therapy is an appropriate treatment option
+Patients 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 above
+Advanced disease (Masaoka staging) not amenable to curative treatment
+Patients eligible for this study should have locally and/or regionally advanced melanoma that is considered potentially surgically resectable and with biopsiable tumor at baseline
+Patients with histologically documented locally advanced, recurrent and/or metastatic NSCLC
+For dose escalation cohort: patients with histologically or cytologically confirmed locally advanced or metastatic solid tumors who have failed at least one line of therapy
+Locally advanced or metastatic pancreatic cancer for the pancreatic cancer cohort
+Locally advanced or metastatic disease not amenable to surgery
+Arms 2, 2E, 3, 3E: patients who previously received > 2 lines of systemic chemotherapy for advanced or metastatic disease
+Locally advanced or metastatic CRC
+RENAL CELL CARCINOMA (RCC) COHORT INCLUSION CRITERIA: History of histologically-proven locally advanced or metastatic (cT2a-T4NanyMany) chromophobe RCC
+Pathologically confirmed advanced pancreatic cancer defined as non-operable in a curative intent, locally recurrent, or metastatic disease
+Patients 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 resectable
+Disease progression after prior therapy in locally advanced or metastatic setting
+In the phase Ib portion, must have locally advanced or metastatic GIST and have progressed on imatinib
+Patients with advanced malignant hepatic tumors.
+Histologically or cytologically documented, incurable, unresectable locally advanced, or metastatic breast cancer
+Have an unresectable, locally advanced pancreatic cancer (AJCC stage III). (Excluded: resectable and borderline resectable patients are ineligible per NCCN criteria)
+Locally advanced or metastatic breast cancer
+Phase II: Patients must have histologically or cytologically confirmed locally advanced, unresectable or metastatic carcinoma of the breast
+Presence of locally advanced, inoperable or metastatic disease
+Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.
+Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.
+Previously treated with one or more regimen of systemic therapy for locally advanced or metastatic disease.
+Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.
+(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.
+For 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 disease
+Patients 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 chemotherapy
+Advanced myelofibrosis
+Histologically or cytologically confirmed diagnosis of metastatic or locally advanced unresectable tumors
+Subject has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to the first dose of study treatment.
+Documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic; patients with documented lymphomas.
+Patients 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;
+Tumor progression during or after first-line treatment for advanced unresectable / metastatic ESCC
+Receipt of 2 or more prior systemic treatments for advanced/metastatic unresectable ESCC
+advanced or metastatic solid tumor (Part A)
+Locally 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).
+Women with histologically or cytologically confirmed breast cancer with evidence of metastatic or locally advanced disease not amenable to any local therapy with curative intent.
+Adult men and women (? 18 years of age) with histologically confirmed diagnosis of metastatic and/or advanced solid tumors not amenable to curative treatment by surgery.
+Patients with histological confirmation of locally advanced or metastatic NSCLC
+Locally advanced lung cancer candidate for curative treatment through radical surgery and/or radio(chemo)therapy
+Prior or concomitant systemic anti-cancer treatment for advanced disease
+Has a pathologically documented advanced/unresectable or metastatic breast cancer
+Part 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).
+Locally recurrent/metastatic.
+All parts except Part B, Part E2, and Part E3 dose expansion: Must have diagnosis of cancer that is advanced or metastatic
+Part E2 dose expansion: must have cancer that is advanced or metastatic and have prior documentation of a mutation of PIK3CA
+Advanced (clinical stage T4b, unresectable) or metastatic disease
+Histologically proven, metastatic or locally advanced non resectable, or recurrent post surgery GIST
+Confirmed locally advanced or metastatic non-small cell lung cancer that is unresectable
+Histologically or cytologically proven metastatic or locally advanced disease. Specifically:
+Subjects who have received up to 3 lines of therapy for advanced disease, without prior exposure to taxane in the advanced stage setting
+Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors that are not amenable for treatment with curative intent
+Progressed after the end of prior aromatase inhibitor therapy for advanced/metastatic breast cancer
+Patients 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.
+Have advanced (not amenable to potentially curative surgery) or metastatic RCC
+Retroperitoneal/hilar adenopathy concerning for locally advanced disease
+Locally advanced (including unresectable or borderline resectable) pancreatic cancer based on computed tomography (CT) imaging, as determined by the principal investigator (PI)
+Advanced metastatic, progressing carcinoid or pancreatic islet cell cancers
+Locally advanced/unresectable (as determined by local surgeon) OR metastatic disease
+Locally advanced (T4b, any N; any T, N2-3) or metastatic (M1) disease as determined by the treating investigator
+Metastatic disease or locally-advanced disease not amenable to curative intent treatment
+Group 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.
+Pathologically confirmed, advanced (unresectable or metastatic):
+Have locally advanced (unresectable) or metastatic small bowel adenocarcinoma
+Unresectable locally advanced or metastatic histologically proven HER2+ gastroesophageal junction (GEJ) or gastric adenocarcinoma.
+Phase 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.
+Patients must have histologically confirmed urothelial carcinoma that is advanced or metastatic
+Patients must have histologically confirmed locally advanced or metastatic pancreas cancer
+Histological 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 disease
+Patients must have histologically or cytologically confirmed advanced leiomyosarcoma of the uterus (ULMS); advanced ULMS is defined as metastatic ULMS or unresectable primary ULMS
+Have metastatic melanoma or NSCLC, or locally advanced NSCLC not suitable for curative-intent local therapy
+PSTAT3 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 study
+Participants 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 study
+-  Histologically or cytologically confirmed metastatic or unresectable locally advanced\n             NSCLC
+No evidence of locally advanced or metastatic disease
+Patients 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)
+Must have locally advanced or distant metastatic disease that is not surgically curable
+Patients with locally advanced bladder cancer based on cross-sectional imaging (suspicion of extravesical disease or hydronephrosis)
+Adult with unresectable locally advanced or metastatic renal cell carcinoma with a clear cell component
+Locally advanced or metastatic malignancy
+TNBC must be either locally recurrent or metastatic; locally recurrent disease must not be amenable to surgical resection or radiation with curative intent
+Biopsy proven locally advanced breast cancer: IIB, IIIA and IIIB
+Patients 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 disease
+PHASE II: Patients must NOT have locally advanced disease
+Patients with advanced malignant solid tumors are excluded
+Locally advanced or metastatic breast cancer
+Histologically proven adenocarcinoma of the breast in the primary or metastatic setting; stage: locally advanced (inoperable) or metastatic
+Diagnosis of advanced stage or metastatic HER2-positive cancer with disease progressed after receiving at least one prior systemic therapy (immunohistochemistry or RT-PCR is used to determine HER2 positivity)
+Advanced or metastatic RCC
+Dose 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.
+Metastatic or locally advanced disease
+No 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).
+Has histologically- or cytologically-confirmed diagnosis of locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma
+Histologic confirmation of advanced solid tumors
+For 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.
+Subject must have received at least 1 prior systemic regimen for advanced or metastatic disease
+Subjects with histological confirmation of locally advanced unresectable or metastatic MSI high CRC.
+Histologically 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.
+Locally advanced breast cancer that is not amenable to curative radiation or surgical cure and/or metastatic disease appropriate for systemic single cytotoxic chemotherapy
+Has received no prior systemic chemotherapy for advanced or metastatic urothelial carcinoma, with the following exceptions:
+unresectable locally advanced recurrent BC or metastatic BC
+Patient has histologically proven advanced (unresectable) or metastatic cancer as outlined below according to study phase and disease type:
+Subjects with histologically confirmed unresectable locally advanced or metastatic adenocarcinoma of the stomach or gastro-esophageal junction (GEJ)
+Prior chemotherapy for unresectable locally advanced or metastatic adenocarcinoma of the stomach or gastro-esophageal junction (GEJ)
+Histologically or cytologically documented, locally advanced or metastatic NSCLC.
+Subjects with histologically confirmed locally advanced or metastatic disease of the following tumor types:
+Inclusion 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 enrollment
+Have histologically or cytologically confirmed, locally advanced or unresectable or metastatic urothelial (transitional cell) carcinoma of the bladder, urethra, ureter, or renal pelvis.
+Locally advanced, relapsed, and/or metastatic cancer
+For 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 expansion
+nab-Paclitaxel and Nivolumab: Subjects must have received 1 prior systemic chemotherapy regimen for locally advanced or metastatic disease.
+Phase 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 benefit
+Phase 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 setting
+Phase II: Post-menopausal female participants with locally advanced or metastatic HER2-negative, hormone receptor-positive breast cancer
+Participants 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 evaluation
+Metastatic or locally-advanced, histologically documented TNBC (absence of HER2, ER, and PR expression)
+Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.
+Phase 1: Subjects with advanced or metastatic solid tumors.
+Histologically 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).
+Subject must have locally advanced or metastatic solid tumor;
+Subjects with any previously treated advanced (metastatic or refractory) solid tumor
+Has not received prior systemic treatment for their advanced/metastatic NSCLC.
+Phase 2 only: Previous treatment with >3 chemotherapy regimens for locally advanced or metastatic disease
+Adult 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.
+Locally 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.
+Histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumors that have a NTRK1, NTRK2, NTRK3, ROS1, or ALK molecular alteration.
+VLA009A: 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.
+Inclusion 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.
+Subjects 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.
+Histologically or cytologically confirmed invasive BC: incurable, unresectable, locally advanced BC previously treated with multimodality therapy or metastatic BC
+Prior 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)
+Progression must have occurred during or after most recent treatment for locally advanced/metastatic BC or within 6 months after completing adjuvant therapy
+Prior 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 disease
+Patients 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 eligible
+Has locally advanced/metastatic disease (i.e., newly diagnosed Stage IV RCC per American Joint Committee on Cancer) or has recurrent disease.
+Presence of advanced malignant hepatic tumors.
+Histologically confirmed locally advanced or stage IV NSCLC
+No more than 2 prior chemotherapies in the advanced or metastatic setting
+Diagnosis of locally advanced or metastatic RCC that is predominantly clear cell histology
+Presence of histologically confirmed inoperable locally advanced or metastatic pancreatic adenocarcinoma
+For 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.
+For Part B: All participants must have a histological evidence of their advanced or metastatic cancer and prescreened alterations in a defined pathway.
+For Part D: All participants must have histological evidence of advanced or metastatic cancer and prescreened alterations in a defined pathway.
+Receipt of prior systemic anti-cancer therapy for unresectable, locally advanced or metastatic melanoma
+Previously received more than 1 regimen of systemic anticancer therapy for locally advanced or metastatic disease.
+Adults with histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction that is inoperable, locally advanced or metastatic and not amenable to curative therapy
+Previous chemotherapy for locally advanced or metastatic gastric cancer.
+Metastatic disease or locally advanced, unresectable disease.
+Patient must have histologically or cytologically confirmed well differentiated or moderately differentiated (low grade or intermediate grade) neuroendocrine tumor that is locally advanced or metastatic and not of pancreatic origin
+Inclusion 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.
+Postmenopausal women with histologically or cytologically confirmed locally advanced or metastatic ER positive breast cancer
+Patients with locally advanced unresectable pancreatic ductal adenocarcinoma are excluded.
+Radiographic and pathologic staging consistent with pancreatic cancer, locally advanced, unresectable (per NCCN criteria)
+Laparoscopic confirmation that PDAC is locally advanced. Biliary stents are permitted
+The subject has metastatic disease or has locally advanced disease that is not amendable to curative treatment
+The 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.
+Adult women (? 18 years of age) with metastatic or locally advanced breast cancer
+Progression while on, or within one month of end of letrozole or anastrozole treatment for locally advanced or metastatic breast cancer.
+Men and women, 18 years or older, with histologically or cytologically-confirmed, advanced solid tumors, Non-Hodgkin Lymphona (NHL), Multiple Myloma (MM), or advanced unresectable solid tumors limited to the tumor types below.
+Have received no prior systemic chemotherapy for advanced/unresectable (inoperable) or metastatic urothelial cancer.
+Histologic confirmation of locally advanced or metastatic RCC with a clear-cell component with or without sarcomatoid features.
+Histologically 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 therapy
+Histologically 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 disease
+Subjects must have histologically confirmed, locally advanced or metastatic solid cancers of the following histological types:
+histopathologically confirmed advanced or metastatic colorectal cancer, excluding primary tumors of appendiceal origin
+Previous systemic therapy for locally advanced or metastatic disease is not allowed.
+For Cohort 2: had prior systemic therapy in the advanced disease setting
+Locally recurrent/metastatic
+Histologically or cytologically documented, locally advanced or metastatic solid tumour, excluding lymphoma, for which standard therapy does not exist or has proven ineffective or intolerable.
+Locally advanced, recurrent, or metastatic incurable solid malignancy with measurable disease per RECIST v1.1
+Histologically-confirmed, locally advanced or metastatic adenocarcinoma of the breast
+Patient has advanced (loco regionally recurrent not amenable to curative therapy, e.g. surgery and/or radiotherapy, or metastatic) breast cancer. Patients may be:
+Patients with histological or cytological proven diagnosis of adenocarcinoma of the breast with evidence of either locally advanced, inoperable and/or metastatic disease
+Patient has advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy
+In the phase Ib portion, must have locally advanced or metastatic GIST and have progressed on imatinib
+Patients with metastatic cancer and/or cancer that is not amenable to surgery (i.e. must be curative intent; locally advanced is acceptable)
+Patients 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 interpretation
+Histologically documented triple-negative adenocarcinoma of the breast that is inoperable locally advanced or metastatic and is not amenable to resection with curative intent
+Any 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 intent
+Histologically 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.
+Locally advanced and/or metastatic disease
+Women 18 years or older with metastatic or locally advanced disease, not amenable to curative therapy
+Biopsy-proven and inoperable locally advanced, recurrent, or metastatic cancer of the esophagus, stomach, or gastro-esophageal junction – adenocarcinoma type
+Metastatic or locally advanced disease that is not amenable to resection or radiation with curative intent.
+Patients must have histologically documented advanced or metastatic adenocarcinoma of the colon or rectum
+Other anticancer therapy for locally advanced or metastatic breast cancer except for prior hormonal therapy.
+Participant has not received prior chemotherapy for metastatic or locally-recurrent and inoperable breast cancer
+Participant has not received prior biologic therapy for metastatic or locally recurrent and inoperable breast cancer
+Locally advanced (T4b, any N; any T, N2-3) or metastatic (M1) disease as determined by the treating investigator
+Histologic 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).
+Histological or cytological diagnosis of metastatic cancer or locally advanced cancer that is not amenable to local therapy
+Histologically-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 indicated
+Histologically-proven, unresectable, locally advanced or metastatic melanoma, SCCHN, NSCLC, and other cancers that express B7-H3.
+Melanoma 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.
+Subjects with cytologically or histologically confirmed locally advanced or metastatic solid tumor malignancy
+In the phase I dose escalation study, must have locally advanced, unresectable or metastatic GIST and have progressed on imatinib
+Concurrent 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)
+Locally advanced unresectable pancreatic cancer by National Comprehensive Cancer Network (NCCN) criteria
+Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor.
+Metastatic or locally recurrent TNBC
+Patients must have a histologically confirmed stage IV or unresectable locally advanced adrenocortical carcinoma
+Received and failed, or were intolerant to, at least 1 prior systemic therapy for locally advanced or metastatic pancreatic ductal adenocarcinoma.
+Unresectable locally advanced or metastatic MPM after locally confirmed progression on 1st line treatment with platinum in combination with pemetrexed.
+Locally unresectable or metastatic carcinoid or pNET
+Measurable metastatic disease or locally advanced and unresectable disease
+Histologically-proven advanced/metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the EGJ
+Patients 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 intent
+Locally advanced (clearly unresectable) or metastatic disease
+Cytologically or histologically confirmed adenocarcinoma of locally advanced or metastatic NSCLC which is not amenable to curative surgery or radiotherapy
+Histologically-proven locally advanced unresectable or metastatic high colorectal carcinoma
+Locally advanced/metastatic NSCLC, not amenable to curative surgery or radiotherapy
+Must have locally advanced or distant metastatic disease that is not surgically curable
+Patients may have received up to one prior line of chemotherapy for metastatic or unresectable locally advanced breast cancer
+The 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.
+Subjects can be treatment naive for metastatic or incurable locally advanced HPV-16 positive solid tumors or can have one prior line of treatment
+i) With at least 1 platinum-containing chemotherapy regimen for metastatic or surgically unresectable locally advanced urothelial cancer, or
+Confirmed metastatic or locally advanced, unresectable disease (by computed tomography [CT] scan or clinical evidence)
+No 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)
+Histologically confirmed diagnosis of advanced (metastatic, recurrent, or unresectable) cancer with mutations in any of the following genes: TSC1, TSC2, NF1, NF2, or STK11
+Histologically confirmed recurrent or metastatic SCCHN; tumor progression or recurrence during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease that must have contained a platinum agent; Patients who have only received chemo-radiation with curative intent for treatment of their locally advanced disease or recurrent disease are not eligible. Patients who received concurrent chemo-radiation as part of treatment of their recurrent disease are also not eligible.
+Histologically or cytologically documented locally advanced or metastatic UBC (including renal pelvis, ureters, urinary bladder, and urethra)
+Disease progression during or following treatment with at least one platinum-containing regimen for inoperable, locally advanced or metastatic UBC or disease recurrence
+Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy.
+Prior treatment with any systemic anti-cancer therapy for locally advanced/metastatic NSCLC.
+Metastatic or locally advanced (unresectable) colorectal cancer with histological confirmation of adenocarcinoma
+Phase I: patients with any locally advanced or metastatic gastrointestinal malignancy which mFOLFOX6 is indicated for treatment
+Histologic proof of metastatic or locally advanced, unresectable breast cancer which is estrogen receptor positive and/or progesterone positive per institutional standards
+Patients must have locally advanced or metastatic predominantly urothelial carcinoma of the bladder, ureter, or urethra that is not amenable to curative surgical treatment
+Locally advanced or metastatic NSCLC
+Patients must have an unresectable locally advanced or metastatic adenocarcinoma
+Patients 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 cancer
+Histologically confirmed PRCC, which is locally advanced or metastatic.
+Documented evidence of NSCLC (locally advanced, unresectable, Stage III)
+Patients 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 eligible
+Histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, urethra)
+Disease 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.
+Have locally advanced disease not amenable to curative treatment by surgery or metastatic disease. In addition, participants must fulfill 1 of the following criteria:
+Have histologically or cytologically confirmed locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) that is anaplastic lymphoma kinase (ALK+).
+Patients with advanced malignant solid tumors are excluded
+Dose Expansion: Chondrosarcoma a. Subjects must have IDH1 gene-mutated chondrosarcoma that is either locally advanced or metastatic and not amenable to complete surgical excision.
+Biopsy proven locally advanced stage cervical cancer (LACC, International Federation of Gynecology and Obstetrics [FIGO] IB2 – IVB)
+Advanced or metastatic cancer
+Histologically 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 setting
+Solid tumor that is metastatic, locally advanced or recurrent
+Women with advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.
+Patients 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 purposes
+Cohort 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 therapy
+Cohort A: patients with histologically proven metastatic or locally advanced MSI colorectal adenocarcinoma
+Cohort B: patients with histologically proven metastatic or locally advanced microsatellite stable (MSS) colorectal adenocarcinoma
+Cohort C: patients with histologically proven metastatic or locally advanced non-colorectal MSI solid tumor malignancies
+Cohort 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)
+Locally advanced or metastatic and/or unresectable Hepatocellular Carcinoma (HCC)
+Must have histological or cytological confirmed diagnosis of locally advanced or metastatic adenocarcinoma of the pancreas, which has progressed on or after one line of chemotherapy
+Inclusion 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 anticoagulation
+Histological 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 defect
+Histological or cytological confirmation of locally advanced or metastatic NSCLC (IIIB-IV)
+Any 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 randomization
+Willing and able to consent for biopsy of locally-advanced or metastatic breast cancer prior to treatment
+Metastatic or locally advanced unresectable breast cancer (includes metastatic or locally advanced unresectable breast cancer which is diagnosed while on adjuvant letrozole or exemestane)
+Locally unresectable or metastatic carcinoid tumors
+Histologically 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 chemotherapies
+Patients 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:
+Patient 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.
+Patients must have received previous treatment with crizotinib for the treatment of locally advanced or metastatic NSCLC.
+Subjects must have metastatic or locally advanced, unresectable cancer; cancer must be “active” (i.e. demonstrable by physical examination, blood tests, or radiographical procedures)
+PK expansion patients: Histologic documentation of locally unresectable or metastatic renal cell carcinoma not currently amenable to surgery, radiation, or other therapy with curative intent
+Previous cytotoxic chemotherapy for advanced (metastatic) disease
+Naïve untreated patients or patients who have progressed on or after any number of prior lines of immunotherapy for unresectable locally advanced or metastatic melanoma
+Previous systemic chemotherapy for unresectable locally advanced or metastatic melanoma.
+Histological or cytological confirmation of locally advanced or metastatic NSCLC (IIIB-IV)
+Patients must be untreated with chemotherapy for metastatic or locally recurrent disease; prior radiation therapy is permitted
+Patients with metastatic or locally advanced, unresectable breast cancer not amenable to curative treatment by surgery or radiotherapy
+Subjects 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 disease
+Advanced/metastatic RCC
+Patients with borderline resectable, locally advanced or metastatic disease.
+Patients must have histologically confirmed adenocarcinoma of colorectal origin that is metastatic or locally advanced and unresectable
+Patients must not have received any prior systemic therapy for metastatic or locally advanced colorectal cancer (CRC); prior VEGF inhibitors are not allowed
+Amendment (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 cohort
+Subjects 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 study
+Presence of metastasized or locally advanced, inoperable (curative intent) at enrollment time, histologically proven, midgut carcinoid tumour (to be centrally confirmed).
+Patients with clinical evidence of locally advanced, nodal, or metastatic bladder cancer
+Patients whose tumors are defined as locally advanced cancer or metastatic cancer are not eligible
+Patients may have received up to one prior line of chemotherapy for metastatic or unresectable locally advanced breast cancer
+Patients with advanced malignant hepatic tumors
+Participants 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 encouraged
+Written 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/or
+Participants with HER2-positive and hormone receptor-positive advanced metastatic or locally advanced breast cancer
+Previous systemic non-hormonal anticancer therapy in the metastatic or locally advanced breast cancer setting
+Advanced or metastatic disease
+Patients 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)
+Dose Expansion phase: Metastatic melanoma (locally advanced or metastatic melanoma)
+Advanced 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 requirement
+For 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 metastatic
+Part D: Breast cancer that is advanced and/or metastatic
+Part E: Melanoma that is advanced and/or metastatic
+Part G: Breast Cancer that is not only advanced and/or metastatic but also hormone receptor positive
+Histologically 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 MPN
+Pathologic confirmation of metastatic or locally advanced RCC with a major clear cell component
+Histologically or cytologically documented advanced or metastatic solid tumors for which established therapy either does not exist or has proven ineffective or intolerable
+Locally advanced/unresectable or metastatic breast cancer
+Histologically or cytologically proven diagnosis of unresectable B3 thymoma or thymic carcinoma recurrent or progressing after more than one prior systemic therapy for advanced / metastatic disease
+Histologically 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)
+Patients 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 registration
+Patients 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 registration
+Prior aromatase inhibitors (e.g. anastrozole, letrozole, exemestane, aminoglutethamide) are allowed in the locally advanced or metastatic setting
+Prior tamoxifen is not allowed in the locally advanced or metastatic setting
+Histologically- 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 urethra
+Histologically 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])
+Has 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)
+Has locally advanced esophageal carcinoma that is resectable or potentially curable with radiation therapy (as determined by local investigator)
+Has had previous therapy for advanced/metastatic adenocarcinoma or squamous cell cancer of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the EGJ
+Cytologically or histologically and radiologically confirmed solid tumor that is inoperable, locally advanced, metastatic, or recurrent:
+Histologically confirmed Papillary Renal Cell Carcinoma, which is unresectable and locally advanced or metastatic with measurable disease as per RECIST 1.1.
+Indication A - ASPS: Histologically proven, unresectable, locally advanced or metastatic alveolar soft part sarcoma.
+Indication B - LMS: Histologically proven, unresectable, recurrent, locally advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular origin and of the bone).
+Indication C - SS: Histologically proven, unresectable, recurrent, locally advanced or metastatic synovial sarcoma.
+Histologically confirmed, chemo-refractory, locally advanced, recurrent or metastatic gastric (including GE junction), colorectal, or pancreatic adenocarcinoma.
+Presumptive or histologically confirmed advanced or metastatic non-curable solid tumor (if limited to a single lesion, and may not be a candidate for curative surgery or radiation therapy).
+Histologically 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.
+Surgically 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).
+Subjects 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 setting
+ErbB-2 positive locally recurrent or metastatic breast cancer
+Patients with advanced malignant hepatic tumors
+Confirmed diagnosis of unresectable, locally advanced or metastatic hereditary or sporadic Medullary Thyroid Cancer.
+Patients must have locally advanced or metastatic urothelial cancer that is not amenable to surgical treatment
+Subject has histologically confirmed locally advanced, metastatic or unresectable Stage IIIB/IV adenocarcinoma NSCLC (newly diagnosed or recurrent). Subjects with mixed histology are eligible if adenocarcinoma is the predominant histology.
+Only locally advanced disease
+Histologically or cytologically confirmed advanced metastatic or unresectable advanced colorectal cancer (CRC) or gastric cancer that is relapsed, refractory, or progressive after:
+Pathologic diagnosis of solid tumor malignancy that is locally advanced or metastatic at time of Screening with documented HER2 expression.
+Histologically or cytologically proved diagnosis of locally advanced recurrent or metastatic non-squamous NSCLC that is not suitable for local curative treatment.
+Patients must have documented locally advanced/metastatic disease, defined by the investigator, which is not amenable to resection with curative intent.
+Histologically or cytologically confirmed metastatic or unresectable locally advanced/metastatic NSCLC
+Advanced adenocarcinoma of the pancreas that is inoperable or metastatic.
+Received more than 1 prior regimen for advanced or metastatic disease.
+Prior radiation to the pelvis or abdomen in the metastatic or locally advanced setting.
+Subject has histologically confirmed locally advanced or unresectable Stage IIIB (not amenable to receive curative treatments such as chemo-radiation)/IV or metastatic NSCLC.
+Advanced (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.
+Has received prior systemic treatment with a taxane for advanced/metastatic disease
+Part 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.
+Patients 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)
+Subject has histologically or cytologically confirmed metastatic or locally advanced, unresectable non-small-cell lung cancer (NSCLC).
+No 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.
+Advanced metastatic disease
+Histologically confirmed and documented previously treated Stage IIIB/IV NSCLC, having failed 1 previous platinum chemo regimen for locally advanced or metastatic disease.
+Failed more than 3 treatment regimens for locally advanced or metastatic NSCLC.
+Metastatic and/or locally advanced malignant solid tumors enriched in tumor types known to be mesothelin expressing
+Histologically confirmed metastatic and/or advanced malignant mesothelin-positive solid tumors as determined by central pathology lab review
+Histological 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.
+Confirmed 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 sorafenib
+Subject 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.
+Histological diagnosis of metastatic or locally advanced inoperable adenocarcinoma of the esophagus, gastroesophageal junction or stomach
+Patients must show signs of progression during or =< 4 months after being treated with a first line therapy for their metastatic or locally advanced inoperable cancer
+Treatment with 1 or more prior chemotherapies for advanced or metastatic adenocarcinoma of the pancreas.
+Treatment with 1 or more prior chemotherapies for advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction.
+For Phase II: Any prior systemic therapy for locally advanced or metastatic melanoma; prior local therapy such as radiation or intratumoral injection is allowed; previous systemic treatment for any stage III disease that was subsequently rendered NED (no evidence of disease) by surgery is allowed
+Received prior treatment with capecitabine or fluoropyrimidine for advanced or metastatic disease
+Advanced adenocarcinoma of the pancreas that is inoperable or metastatic.
+Received more than 1 prior regimen for advanced or metastatic disease.
+Previous systemic therapy for advanced or metastatic disease.
+No prior chemotherapy for locally advanced or metastatic disease
+Subjects 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:
+Received at least two prior systemic cytotoxic chemotherapy regimens for unresectable, locally advanced or metastatic disease.
+At 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:
+Diagnosis of locally advanced or metastatic liver cancer obtained by histology/cytology or by imaging
+Diagnosis of breast cancer with evidence of a) metastatic or b) locally recurrent/advanced disease.
+Patient 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 ineligible
+Patient has localized resectable, locally advanced unresectable or advanced metastatic disease; patients with adenocarcinoma of the pancreatic body or tail are ineligible
+Metastatic disease as documented by CT scan or MRI (locally advanced disease only NOT eligible)
+Females 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 laboratory
+Locally advanced or inflammatory breast cancer (stage IIIA to IIIC)
+Previous chemotherapy for locally advanced or metastatic disease
+PANCREATIC 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/NCI
+Evidence of locally advanced, metastatic, muscle-invasive, and/or extravesical bladder cancer
+Histologically confirmed, unresectable locally advanced or metastatic transitional cell carcinoma of the urothelium
+Prior chemotherapy for metastatic or locally recurrent disease Exceptions:
+Prior immunotherapy for metastatic or locally recurrent disease
+Part 2a, Part 2c, and Part 2f (GIST patients): Histologically confirmed locally advanced, metastatic and/or unresectable GIST.
+Locally advanced or metastatic solid tumors;
+Patient has locally recurrent or metastatic disease
+Histologic 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 disease
+Subjects 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, and
+Have advanced or metastatic cancer and be an appropriate candidate for experimental therapy.
+Histologically or cytologically documented, locally advanced or metastatic solid tumors for which standard therapy either does not exist or has proven ineffective or intolerable
+No more than four prior systemic therapies for locally advanced or metastatic cancer
+Subjects 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).
+Locally advanced or inflammatory cervical or uterine cancer
+Histologically or cytologically documented advanced or metastatic solid tumors for which established therapy either does not exist or has proven ineffective or intolerable
+Histologically confirmed, locally advanced, not amenable to curative therapy, or metastatic non-small cell lung cancer (NSCLC)
+Participants 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 disease
+Histologically or cytologically confirmed locally advanced or metastatic urothelial carcinoma (UC)
+No prior systemic therapy for inoperable locally advanced or metastatic UC
+Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with EGFR activating mutation (excluding exon 20 insertion); measurable disease per RECIST 1.1
+Histologically or cytologically documented unresectable, locally advanced or metastatic breast cancer or gastric cancer refractory to standard therapy.
+Subjects must have metastatic or unresectable locally advanced malignant solid tumor.
+Patients with advanced malignant solid tumors
+Diagnosis of NSCLC with locally advanced or metastatic disease
+Have 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 therapy
+Age = or > 18 years Histological or cytological diagnosis of undifferentiated or poorly differentiated nasopharyngeal carcinoma that is locally advanced or metastatic.
+Part A: Histological or cytological confirmation of a solid tumor and disease progression. Part B: Histological or cytological confirmation of ER positive, HER2 negative breast cancer and disease progression or any other solid tumor with a PIK3CA gene mutation. Part C: Histological or cytological confirmation of ER positive, HER2 negative postmenopausal breast cancer with locally advanced or metastatic disease that is eligible for fulvestrant treatment. Part D: Histological or cytological confirmation of ER positive, HER2 negative postmenopausal breast cancer with locally advanced or metastatic disease that is eligible for fulvestrant treatment. Patients must also present with a tumor related mutation of the PIK3CA gene.
+Metastatic or locally advanced disease
+Have advanced or metastatic cancer and be an appropriate candidate for experimental therapy.
+Patient 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.
+Patient 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.
+Patients 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)
+Cytologically or histologically confirmed advanced gastric or GEJ adenocarcinoma that is metastatic or locally advanced and unresectable.
+Metastatic or locally advanced disease not amenable to curative surgery and/or radiotherapy
+Subjects with advanced/metastatic Colorectal Cancer(CRC) who have failed or been intolerant to both irinotecan- and oxaliplatin- based regimens
+Documented radiographic disease progression following at least one line of therapy in the advanced/metastatic setting
+Locally advanced or metastatic disease
+Prior systemic therapy for locally advanced or metastatic hepatocellular cancer
+Histologically confirmed, locally advanced or metastatic HCC.
+Inoperable metastatic or locally advanced unresectable disease
+Histological documentation of incurable, locally advanced, or metastatic non-squamous
+Locally advanced or metastatic solid KRAS-mutant tumors, for which standard therapies do not exist, have proven ineffective or intolerable or are considered inappropriate
+Presence of locally advanced or metastatic disease with at least one measurable lesion.
+Prior treatment with more than two regimens of systemic cytotoxic chemotherapy for locally recurrent or metastatic disease
+Patients must have evidence of recurrent, locally advanced, or metastatic disease.
+For 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 intent
+Patients with a documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic.
+For 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 NSCLC
+Received no prior chemotherapy for advanced or metastatic disease (Part 2 and Part 2a)
+Subjects with histologically confirmed, locally advanced or metastatic, refractory solid tumors who are not candidates for standard therapy
+Treatment with at least two prior systemic therapies for advanced (unresectable locoregional or metastatic) disease
+Metastatic or unresectable locally advanced/recurrent breast cancer
+Previous radiotherapy for the treatment of unresectable, locally advanced/recurrent or metastatic breast cancer is not allowed if:\r\n* The last fraction of radiotherapy has been administered within 14 days of first on-study thormbokinetic study\r\n* The patient has not recovered from any resulting acute toxicity (to grade =< 1) prior to first on-study thormbokinetic study
+Locally advanced basal cell carcinoma lesion that is considered to be inoperable or to have medical contraindications to surgery
+Patients must have histologically confirmed breast cancer that is:\r\n* Metastatic; OR\r\n* Incurable and locally advanced, as determined by the treating physician
+Patients 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 lesion
+Stage IV disease or inoperable locally advanced disease.
+Receipt of 2 or more prior cytotoxic chemotherapy regimens for advanced, recurrent, or metastatic endometrial cancer.
+Patients with a documented (histologically- or cytologically-proven) epithelial cell/adenocarcinoma of the pancreas that is relapsed, locally advanced, or metastatic.
+Subject with more than 2 prior cytotoxic therapies (not including treatment administered for locally curable disease) for unresectable or metastatic gastroesophageal adenocarcinoma.
+Known advanced malignant hepatic tumors
+Histologically 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)
+Subjects with advanced or metastatic solid tumors for whom a chemotherapy regimen is considered appropriate
+Presence of locally advanced or metastatic disease with at least one measurable lesion.
+Prior hormonal therapy for locally advanced or metastatic disease is allowed but this must have been discontinued prior to enrollment; no washout period will be required
+Histologically confirmed GIST that is locally advanced or metastatic
+Women 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 intent
+Any previous chemotherapy for inoperable locally advanced or metastatic TNBC or HR+/HER2- adenocarcinoma of the breast (patients receiving neo/adjuvant chemotherapy eligible provided they have at least a 12 month disease-free interval)
+Inclusion 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.
+Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.
+Phase 1: Subjects with advanced or metastatic solid tumors.
+Phase 2: Subjects with advanced or metastatic urothelial carcinoma or RCC.
+Breast cancer that is locally advanced or metastatic
+More than 1 prior chemotherapy given for locally advanced or metastatic disease
+Dose 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:
+Patients with confirmed HER-2 positive, metastatic or non-operable locally advanced breast or gastric cancer
+Measurable 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 cervix
+Prior 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 enrollment
+Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally advanced disease not amenable to curative resection
+Previous systemic non-hormonal anti-cancer therapy in the metastatic or locally advanced breast cancer setting
+Histologically or cytologically documented, locally advanced or metastatic solid tumors or lymphoma for which standard therapy either does not exist or has proven ineffective or intolerable
+More than two regimens of cytotoxic chemotherapy for the treatment of locally advanced or metastatic cancer
+Postmenopausal women with HER2-, HR+ locally advanced or metastatic breast cancer
+Previous chemotherapy for locally advanced or metastatic breast cancer
+Patients with advanced cutaneous or subcutaneous in-transit or metastatic melanoma
+Cytological 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)
+Histologically 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 cancer
+Histologic 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 cancer
+Progressive disease within three months of completion of curatively intended treatment for locoregionally advanced or metastatic HNSCC
+Histologically 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 occur
+Documented 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.
+Part A- Diagnosed with advanced and/or metastatic cancer during dose escalation
+Unresectable locally advanced or metastatic HCC;
+Have 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.
+Metastatic or locally advanced unresectable RCC. NOTE: Prior nephrectomy is not mandatory.
+Confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease
+Histologically or cytologically confirmed, locally advanced or metastatic squamous NSCLC
+Subject has histologically or cytologically confirmed metastatic or locally advanced, unresectable solid tumors harboring EGFR mutations.
+Patients must have progressed during or after at least one previous systemic, anti-cancer treatment for locally advanced or metastatic NSCLC.
+Patients 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 participation
+PATIENT: Diagnosed with advanced non-small cell lung carcinoma (NSCLC) being treated with non-curative intent, and informed of advanced disease within the prior eight weeks
+Locally recurrent or metastatic breast cancer
+Participants 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.
+Locally advanced, recurrent, or metastatic, PIK3CA mutant, incurable solid tumor malignancy, including breast cancer Stages I and II, Arm B:
+Postmenopausal female participants with histologically documented locally advanced or metastatic PIK3CA-mutant HR+/HER2- breast cancer
+Postmenopausal female participants with locally advanced or metastatic PIK3CA-mutant HR+/HER2? breast cancer Stages I and II:
+Patients with metastatic and/or advanced solid tumors or lymphomas not amenable to curative treatment by surgery.
+Histologically documented advanced or metastatic solid tumors or lymphomas
+Patients must have at least 1 standard treatment regimen in the advanced, recurrent or metastatic setting
+Advanced or metastatic breast cancer
+Diagnosis of histologically-confirmed esophageal, gastric, pancreatic, or colorectal that is metastatic or locally-advanced (unresectable)
+Patient is at least 3 weeks post-diagnosis of an incurable (locally advanced or metastatic) solid malignancy
+Advanced, incurable cancer
+PATIENTS: Diagnosis of advanced cancer (defined as locally advanced, metastatic recurrent, or incurable disease)
+Patients 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 indicated
+Definition of advanced cancer includes those patients who have metastatic or refractory disease according to their treating oncologist
+Have borderline resectable or unresectable locally advanced disease or metastatic disease
+Intraoperative evidence of metastatic or locally-unresectable disease
+Advanced rheumatoid arthritis
+Presence of residual or recurrent cancer (locally or metastatic)
+Diagnosis of locally advanced, recurrent, or metastatic disease.
+Patients with advanced cancer (locally advanced, metastatic, recurrent and/or incurable cancer)
+Patients with diagnosis of advanced cancer, including recurrent, locally advanced, or metastatic cancer
+Patients with locally advanced surgically unresectable PDAC
+Histologically or cytologically confirmed locally advanced or metastatic adenocarcinoma of the stomach or GEJ in participants who have not received prior systemic therapy for metastatic disease
+Patients with only locally advanced disease
+Subjects must have histologic documentation of advanced recurrent or metastatic cancer.
+Subjects must be at the recurrent/metastatic setting, with selected advanced solid tumors.
+Advanced unresectable or metastatic disease
+Histologically 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 therapy
+Histologically documented advanced or metastatic solid tumors.
+Pathologically 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 documented
+Unresectable, locally advanced or metastatic disease; diagnosed within 6 weeks prior to screening
+Prior treatment of pancreatic cancer in the metastatic setting (or locally advanced setting) with surgery (placement of stent is allowed), radiotherapy, chemotherapy or investigational therapy
+Metastatic or locally recurrent unresectable breast cancer
+Diagnosis of advanced cancer (defined as locally advanced, metastatic, recurrent, or incurable disease)
+Locally recurrent or metastatic disease
+Patients who have been diagnosed with locally advanced unresectable NSCLC undergoing definite chemo-radiation with curative intent
+Locally advanced breast cancer patients treated with surgery and adjuvant radiation
+No 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 registration
+Have 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 disease
+Phase 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.
+No 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.
+Locally advanced disease which is unresectable, or resectable but suitable for an organ sparing approach
+Documented disease recurrence or disease progression of: (a) locally advanced disease that is not considered curable by surgery and/or radiation; or (b) metastatic disease.
+Adult women > 18 years of age with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy
+Patients presenting with locally advanced disease in the breast (cT4) and/or in the nodes (cN2/N3) as assessed by clinical exam and imaging
+Patients with histologically confirmed pancreatic adenocarcinoma (borderline resectable or locally advanced disease at presentation) are eligible for the study
+Histologically confirmed, locally-advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) or other malignancies known to express CA19-9 positive malignancies
+Histologically confirmed cancer that is advanced; metastatic; or otherwise not suitable for surgical resection with curative intent
+Patients who have known metastatic disease or other locally advanced disease in the thoracic or cervical regions
+Patient with advanced skin cancers
+Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation
+Subject has histologically or cytologically documented diagnosis of pancreatic adenocarcinoma with metastatic disease. Locally advanced subjects are not eligible.
+Patients 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.
+Dose 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.
+Locally advanced or metastatic, unresectable sarcoma that has progressed after treatment with 150 mg/m2 or less of doxorubicin or anthracycline equivalent
+Locally advanced breast cancer, defined as being clinically appropriate for neoadjuvant chemotherapy
+Subject 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 study
+Patients with metastatic or locally unresectable PDAC* (resectability is as defined by MSKCC pancreatic surgeon)
+Have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic
+Patients with histologic or cytologic diagnosis of advanced or metastatic solid tumors or lymphomas for which no curative or life-prolonging therapies exist.
+Histological or cytological confirmation of an ER+ advanced metastatic breast cancer tumour that is eligible for treatment with fulvestrant
+Advanced cancer diagnosis (locally advanced, recurrent or metastatic disease)
+Patients with a diagnosis of advanced cancer, including recurrent, locally advanced, or metastatic cancer
+Patients with the diagnosis of advanced cancer defined as locally advanced, recurrent or metastatic disease
+Diagnosis of advanced cancer, defined as locally advanced, recurrent or metastatic disease
+Hormone therapy for locally advanced disease (except patients on 5-alpha reductase inhibitors to reduce the size of the prostate)
+No more than 3 total prior systemic treatment regimens in the advanced or metastatic setting
+Histologically or cytologically documented, locally advanced or metastatic solid tumors for which standard therapy either does not exist or has proven ineffective or intolerable
+Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.
+Part 1: Subjects with advanced or metastatic solid tumors.
+Participants 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 unresectable
+No prior chemotherapy for inoperable locally advanced or mUC
+Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent
+Part 1: Subjects with advanced or metastatic solid tumors
+Advanced 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.