Metastatic disease or locally advanced disease that is not resectable. 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 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. Must have failed at least prior treatment regimen for locally advanced or metastatic disease or be intolerant to treatment or refuse standard treatment Locally advanced or metastatic HER-positive breast cancer that has relapsed or is refractory to established therapies In the dose expansion phase, Arm A will be open for 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 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 EHE patients will be accrued on this study Prior chemotherapy or any other investigational agents for the treatment of locally advanced or metastatic pancreatic cancer Histologically confirmed locally advanced melanoma (pembrolizumab only), metastatic NSCLC (pembrolizumab only) locally advanced or metastatic urothelial carcinoma (atezolimumab only). No prior chemotherapy or targeted systemic therapy (including endocrine therapy) for inoperable locally advanced or metastatic TNBC Progressive metastatic or locally advanced or metastatic breast cancer. 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 prior approved regimen for locally advanced or metastatic disease followed by documented progressive disease. All subjects must have previously treated either locally advanced or metastatic renal or urothelial cell carcinoma to be eligible for participation Locally advanced or metastatic NSCLC 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. Refractory or intolerant to at least one prior standard therapy(ies) for metastatic or locally advanced disease. Patients must have locally advanced, metastatic or refractory leiomyosarcoma or dedifferentiated liposarcoma 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). 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 (T) 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 p(-) locally/regionally advanced (T? or N?) oropharyngeal cancer\r\n* HPV(+) or p(+) locally/regionally advanced (T or N) oropharyngeal cancer\r\n* T or T laryngeal or hypopharyngeal cancer that is locally advanced, bulky (> 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 T? and/or N) nasopharyngeal cancer which is EBV (-) (Epstein?Barr virus) 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 . at least cm with contrast enhanced dynamic imaging (magnetic resonance imaging or computed tomography) Sign of locally advanced disease or metastatic bladder cancer Diagnosed with (a) locally advanced or metastatic (stage III-IV) breast cancer or (b) advanced prostate cancer Biopsy proven locally advanced or metastatic prostate cancer. Patients should have had either progression during or after at least two HER-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/non-operable or metastatic breast cancer that has not been previously treated in the metastatic setting with systemic therapy (i.e. first line treatment) Evidence of locally advanced or metastatic disease; 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 =< cm; locally advanced disease defined as: T -N+MO or T- NxMo, or borderline resectable and unresectable adenocarcinoma without distant metastatic disease or resectable T- NxMo disease or M with controlled distant disease Locally advanced disease that is not resectable or metastatic disease. Patients with borderline resectable, locally advanced or metastatic disease 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 months after completion of adjuvant therapy Received > prior systemic anti-cancer drug regimen for locally advanced disease 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 Metastatic or locally advanced breast cancer for which endocrine therapy is an appropriate treatment option Locally advanced or metastatic CRC 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 Stage IV or locally advanced cancers for which no alternative therapies with proven survival advantage are available Locally advanced or metastatic breast cancer 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. Patients with histologically proven small cell carcinoma of the bladder, or elsewhere along the urothelium, which is locally advanced or metastatic (i.e. > or = cTb, > or = pTb, N+, or M+) at the time of presentation or cystectomy who have been treated with chemotherapy Locally advanced (Tb, any N; or any T, N ?) or metastatic disease (any T, any N and M). Locally advanced bladder cancer must be unresectable i.e. invading the pelvic or abdominal wall (stage Tb) or presenting with bulky nodal disease (N-). Patients with histological confirmation of locally advanced or metastatic NSCLC Retroperitoneal/hilar adenopathy concerning for locally advanced disease Locally advanced (Tb, any N; any T, N-) or metastatic (M) disease as determined by the treating investigator Patients with locally advanced disease who are candidates for other preoperative chemotherapy at the time of initial evaluation; this may include patients with locally advanced disease such as:\r\n* Inflammatory breast cancer (Td)\r\n* Fixed axillary lymph node metastases (N)\r\n* Metastasis to ipsilateral internal mammary node (N) No evidence of locally advanced or metastatic disease 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) Locally advanced or metastatic malignancy PHASE II: Patients must NOT have locally advanced disease Locally advanced or metastatic breast cancer Histologically proven adenocarcinoma of the breast in the primary or metastatic setting; stage: locally advanced (inoperable) or metastatic Metastatic or locally advanced disease Locally advanced, relapsed, and/or metastatic cancer Phase II: Post-menopausal female participants with locally advanced or metastatic HER-negative, hormone receptor-positive breast cancer Phase only: Previous treatment with > chemotherapy regimens for locally advanced or metastatic disease VLAA: 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. VLAB: locally advanced and/or metastatic disease and judged to be a candidate for pembrolizumab to be used in combination with CVA. Progression must have occurred during or after most recent treatment for locally advanced/metastatic BC or within months after completing adjuvant therapy Previously received more than regimen of systemic anticancer therapy for locally advanced or metastatic disease. Previous chemotherapy for locally advanced or metastatic gastric cancer. 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 Adult women (? 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. Previous systemic therapy for locally advanced or metastatic disease is not allowed. In the phase Ib portion, must have locally advanced or metastatic GIST and have progressed on imatinib 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 (>/=) months prior to Cycle Day . Locally recurrent disease must not be amenable to resection with curative intent Stage IV or locally advanced cancers for which no alternative therapies with proven survival advantage are available Locally advanced and/or metastatic disease Other anticancer therapy for locally advanced or metastatic breast cancer except for prior hormonal therapy. Locally advanced (Tb, any N; any T, N-) or metastatic (M) disease as determined by the treating investigator 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) Unresectable locally advanced or metastatic MPM after locally confirmed progression on st line treatment with platinum in combination with pemetrexed. Must have locally advanced or distant metastatic disease that is not surgically curable Prior treatment with any systemic anti-cancer therapy for locally advanced/metastatic NSCLC. Phase I: patients with any locally advanced or metastatic gastrointestinal malignancy which mFOLFOX is indicated for treatment Locally advanced or metastatic NSCLC Patients whose esophageal or GEJ cancer has become metastatic or unresectable locally advanced within months of completing definitive therapy for localized or locally advanced cancer can be considered as having received one line of therapy for advanced cancer Willing and able to consent for biopsy of locally-advanced or metastatic breast cancer prior to treatment Patients must have received previous treatment with crizotinib for the treatment of locally advanced or metastatic NSCLC. Patients with borderline resectable, locally advanced or metastatic disease. 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 Participants with HER-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 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 weeks prior to registration Patients must not have had more than 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 weeks prior to study registration Prior tamoxifen is not allowed in the locally advanced or metastatic setting Patients must have locally advanced or metastatic urothelial cancer that is not amenable to surgical treatment Only locally advanced disease 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) No more than three prior anticancer regimens (BRAF/MEK inhibitors, IL- or investigational agents) including no more than one chemotherapy-containing regimen for advanced (recurrent, locally advanced or metastic) disease. Failed more than treatment regimens for locally advanced or metastatic NSCLC. Patients with locally advanced BCC are required to have disease that is considered inoperable due to significant functional compromise or to have a medical contraindication to surgery Patients must show signs of progression during or =< months after being treated with a first line therapy for their metastatic or locally advanced inoperable cancer No prior chemotherapy for locally advanced or metastatic disease Diagnosis of locally advanced or metastatic liver cancer obtained by histology/cytology or by imaging 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 (HER-) negative, and Ki (a tumor marker) ? % determined by the central study laboratory Previous chemotherapy for locally advanced or metastatic disease Evidence of locally advanced, metastatic, muscle-invasive, and/or extravesical bladder cancer 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 No more than four prior systemic therapies for locally advanced or metastatic cancer Locally advanced or inflammatory cervical or uterine cancer No prior systemic therapy for inoperable locally advanced or metastatic UC Diagnosis of NSCLC with locally advanced or metastatic disease Metastatic or locally advanced disease Locally advanced or metastatic disease Prior systemic therapy for locally advanced or metastatic hepatocellular cancer Histological documentation of incurable, locally advanced, or metastatic non-squamous Presence of locally advanced or metastatic disease with at least one measurable lesion. 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 Breast cancer that is locally advanced or metastatic More than prior chemotherapy given for locally advanced or metastatic disease Patients with confirmed HER- positive, metastatic or non-operable locally advanced breast or gastric cancer Previous systemic non-hormonal anti-cancer therapy in the metastatic or locally advanced breast cancer setting More than two regimens of cytotoxic chemotherapy for the treatment of locally advanced or metastatic cancer Postmenopausal women with HER-, HR+ locally advanced or metastatic breast cancer Previous chemotherapy for locally advanced or metastatic breast cancer Documented evidence of advanced (locally recurrent, locally advanced and/or metastatic) adipocytic (restricted to subtypes listed in Inclusion ) or leiomyosarcoma, incurable by surgery and/or radiotherapy. 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 Postmenopausal female participants with histologically documented locally advanced or metastatic PIKCA-mutant HR+/HER- breast cancer Postmenopausal female participants with locally advanced or metastatic PIKCA-mutant HR+/HER? breast cancer Stages I and II: PATIENTS: Diagnosis of advanced cancer (defined as locally advanced, metastatic recurrent, or incurable 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 only locally advanced disease Diagnosis of advanced cancer (defined as locally advanced, metastatic, recurrent, or incurable disease) Locally advanced breast cancer patients treated with surgery and adjuvant radiation 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. 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. Patients presenting with locally advanced disease in the breast (cT) and/or in the nodes (cN/N) as assessed by clinical exam and imaging Patients who have known metastatic disease or other locally advanced disease in the thoracic or cervical regions Hormone therapy for locally advanced disease (except patients on -alpha reductase inhibitors to reduce the size of the prostrate) 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 months before the data of study entry. Locally advanced breast cancer, defined as being clinically appropriate for neoadjuvant chemotherapy 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 -alpha reductase inhibitors to reduce the size of the prostate) Locally advanced or metastatic head and neck cancer. 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