Patients must have histologically confirmed epithelioid hemangioendothelioma which is metastatic or locally advanced (unresectable)
Must have histologically confirmed advanced CRC that is metastatic.
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).
Histologically confirmed locally advanced melanoma (pembrolizumab only), metastatic NSCLC (pembrolizumab only) locally advanced or metastatic urothelial carcinoma (atezolimumab only).
Histologically confirmed breast adenocarcinoma that is unresectable loco-regionally advanced or metastatic.
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.
PHASE IB: Histologically confirmed refractory locally-advanced unresectable or metastatic pancreatic or biliary cancer
Patients with advanced and/or metastatic, histologically documented solid tumors.
Phase 1: Patients with histologically or cytologically confirmed locally advanced (unresectable) or metastatic solid tumors and with progressive disease during or after treatment with a PD-1 or PD-L1-inhibitor who meet one of the following criteria:
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
Have histologically confirmed, locally advanced unresectable or metastatic (stage IV) colorectal adenocarcinoma
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
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.
Female patients with histologically-confirmed, unresectable locally advanced or metastatic breast cancer;
Patients must have histologically confirmed breast cancer that is metastatic or locally advanced and unresectable
Subjects must have a histologically confirmed metastatic and/or locally advanced sarcoma
Histologically confirmed diagnosis of metastatic or advanced unresectable tumors that progressed on standard therapy
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
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
Stage IV or locally advanced histologically confirmed solid tumors for which no alternative therapies with proven survival advantage are available
Histologically documented non-keratinizing locally advanced recurrent or metastatic NPC.
Histologically and radiologically confirmed advanced metastatic CCRCC in patients who have had at least one prior systemic therapy, which can include axitinib
Advanced malignancies (except leukemias), histologically proven at diagnosis; Histologically confirmed advanced malignancies that are known to be sensitive to PF-03241066 inhibition, e.g. ALK, c-MET and ROS
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-confirmed, mesothelin-expressing metastatic or advanced non-metastatic disease (tumour type specific inclusion criteria)
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
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;
Histologically proven, metastatic or locally advanced non resectable, or recurrent post surgery GIST
Patients must have histologically confirmed locally advanced or metastatic pancreas cancer
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)
Histologically proven adenocarcinoma of the breast in the primary or metastatic setting; stage: locally advanced (inoperable) or metastatic
Patient has histologically proven advanced (unresectable) or metastatic cancer as outlined below according to study phase and disease type:
Subjects with histologically confirmed locally advanced or metastatic disease of the following tumor types:
Metastatic or locally-advanced, histologically documented TNBC (absence of HER2, ER, and PR expression)
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).
Histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumors that have a NTRK1, NTRK2, NTRK3, ROS1, or ALK molecular alteration.
Histologically or cytologically confirmed invasive BC: incurable, unresectable, locally advanced BC previously treated with multimodality therapy or metastatic BC
Histologically confirmed inoperable advanced adenocarcinoma of the colon or rectum
Histologically confirmed inoperable advanced adenocarcinoma of the colon or rectum
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:
Histologically confirmed unresectable advanced or recurrent esophageal cancer
Histologically-confirmed, locally advanced or metastatic adenocarcinoma of the breast
Patients must have histologically documented advanced or metastatic adenocarcinoma of the colon or rectum
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.
Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor.
Patients must have a histologically confirmed stage IV or unresectable locally advanced adrenocortical carcinoma
Histologically-proven advanced/metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the EGJ
Histologically-proven locally advanced unresectable or metastatic high colorectal carcinoma
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 PRCC, which is locally advanced or metastatic.
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
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)
Patients must have histologically confirmed adenocarcinoma of colorectal origin that is metastatic or locally advanced and unresectable
Presence of metastasized or locally advanced, inoperable (curative intent) at enrollment time, histologically proven, midgut carcinoid tumour (to be centrally confirmed).
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
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])
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.
Confirmed diagnosis of unresectable, locally advanced or metastatic hereditary or sporadic Medullary Thyroid Cancer.
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.
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
Histologically confirmed, unresectable locally advanced or metastatic transitional cell carcinoma of the urothelium
Part 2a, Part 2c, and Part 2f (GIST patients): Histologically confirmed locally advanced, metastatic and/or unresectable GIST.
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)
Histologically confirmed, locally advanced or metastatic HCC.
Subjects with histologically confirmed, locally advanced or metastatic, refractory solid tumors who are not candidates for standard therapy
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
Histologically confirmed GIST that is locally advanced or metastatic
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
Histologically documented advanced or metastatic solid tumors or lymphomas
Diagnosis of histologically-confirmed esophageal, gastric, pancreatic, or colorectal that is metastatic or locally-advanced (unresectable)
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.
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
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.
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.