Pembrolizumab Plus Lenvatinib in Combination With Belzutifan in Solid Tumors (MK-6482-016)
Carcinoma, Hepatocellular, Colorectal Neoplasms, Pancreatic Ductal Adenocarcinoma
About this trial
This is an interventional treatment trial for Carcinoma, Hepatocellular
Eligibility Criteria
Inclusion Criteria:
Diagnosis of one of the following advanced (unresectable and/or metastatic) solid tumors, documented by histopathology or cytopathology:
- Hepatocellular carcinoma (HCC)
- Colorectal cancer (CRC) (non-microsatellite instability-high [non-MSI-H]/deficient mismatch repair [dMMR])
- Pancreatic ductal adenocarcinoma (PDAC).
- Biliary tract cancer (BTC) (includes intrahepatic, extrahepatic cholangiocarcinoma [CCA] and gall bladder cancer)
- Endometrial cancer (EC)
- Esophageal squamous cell carcinoma (ESCC)
- Disease progression on or since the most recent treatment (does not apply to newly diagnosed unresectable or metastatic HCC or EC).
- Measurable disease per RECIST v1.1 as assessed locally (by investigator) and verified by BICR
- Submission of an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
- Male participants are abstinent from heterosexual intercourse or agree to follow contraceptive guidance during and for at least 7 days after last dose of study intervention with belzutifan and lenvatinib
- Female participants are not pregnant or breastfeeding, not a woman of child-bearing potential (WOCBP), or is a WOCBP and agrees to follow contraceptive guidance during the intervention period and and for at least 120 days after the last dose of pembrolizumab or for at least 30 days after last dose of lenvatinib or belzutifan, whichever occurs last
- Adequate organ function
- Adequately controlled blood pressure with or without antihypertensive medications
- HCC Specific Inclusion Criteria: No prior systemic chemotherapy, including anti-VEGF therapy, anti-programmed cell-death (PD-1)/PD-L1 or any systemic investigational anticancer agents for advanced/unresectable HCC (1L)
- CRC ([non-MSI-H/dMMR) Specific Inclusion Criteria: Received at least 2 prior lines of systemic therapy for unresectable or metastatic disease which includes fluoropyrimidine, irinotecan and oxaliplatin
- PDAC Specific Inclusion Criteria: Prior therapy with at least 1 (platinum or gemcitabine containing regimen) but no more than 2 prior systemic therapies for unresectable or metastatic pancreatic cancer
- BTC Specific Inclusion Criteria: Received at least 1 prior line of systemic therapy (containing gemcitabine or fluoropyrimidine) for unresectable or metastatic disease
- EC Specific Inclusion Criteria: Study treatment is for 1L therapy of EC and participants should not have received prior systemic chemotherapy. Exception: May have received 1 prior line of line of systemic platinum-based adjuvant and/or neoadjuvant chemotherapy in the setting of a curative-intent resection, if the recurrence occurred ≥6 months after the last dose of chemotherapy or may have received prior radiation with or without chemotherapy
- ESCC Specific Inclusion Criteria: Have experienced radiographic or clinical progression on one prior line of standard systemic therapy (immune oncology (IO) naïve participants) or an anti-PD-1/PD-L1 (IO resistant participants)
Exclusion Criteria:
- Unable to swallow orally administered medication or presence of a gastrointestinal (GI) disorder that may affect study intervention absorption
- History of a second malignancy that is progressing or has required active treatment within 3 years
- A pulse oximeter reading <92% at rest, or requirement of intermittent supplemental oxygen/ chronic supplemental oxygen
- Presence of central nervous system (CNS) metastases and/or carcinomatous meningitis
- Clinically significant cardiovascular disease within 6 months of first dose of study intervention
- Symptomatic pleural effusion, unless clinically stable after treatment
- Preexisting ≥ Grade 3 gastrointestinal (GI) or non-GI fistula
- Moderate to severe hepatic impairment
- Clinically significant history of bleeding within 3 months before screening
- Presence of serious active nonhealing wound/ulcer/bone fracture
- Requirement for hemodialysis or peritoneal dialysis
- History of human immunodeficiency virus (HIV) infection
- History of Hepatitis B or active Hepatis C virus infections. with exceptions for HCC and BTC
- Prior therapy with a PD-1, anti-PD-L1, anti-PD-L2 agent, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) or hypoxia-inducible factor 2α (HIF-2α)
- Radiographic evidence of intratumoral cavitation, or invasion/infiltration of a major blood vessel
- EC specific exclusion criteria: History of carcinosarcoma, endometrial leiomyosarcoma or other high-grade sarcomas, or endometrial stromal sarcomas
- ESCC specific exclusion criteria: Has clinically apparent ascites or pleural effusion or experienced weight loss >20% over approximately 3 months before first dose of study therapy
Sites / Locations
- University of Arizona Cancer Center-University of Arizona Cancer Center - North Campus ( Site 5047)Recruiting
- City of Hope Comprehensive Cancer Center ( Site 5002)
- Cedars-Sinai Medical Center ( Site 5045)Recruiting
- UCSF Medical Center at Mission Bay ( Site 5021)Recruiting
- Yale-New Haven Hospital-Yale Cancer Center ( Site 5013)Recruiting
- Sibley Memorial Hospital ( Site 5051)Recruiting
- University of Florida College of Medicine ( Site 5015)Recruiting
- Johns Hopkins Hospital-Sidney Kimmel Comprehensive Cancer Center - GI and Immunology ( Site 5048)Recruiting
- Memorial Sloan Kettering Cancer Center ( Site 5050)Recruiting
- Duke Cancer Institute ( Site 5026)Recruiting
- University of Texas MD Anderson Cancer Center-Gastrointestinal Medical Oncology ( Site 5049)Recruiting
- Inova Schar Cancer Institute ( Site 5039)Recruiting
- Blue Ridge Cancer Care ( Site 5053)Recruiting
- Northwest Medical Specialties, PLLC ( Site 5025)Recruiting
- University of Wisconsin Hospitals and Clinics ( Site 5037)Recruiting
- Gosford Hospital-Oncology Trials ( Site 4004)Recruiting
- Westmead Hospital-Department of Medical Oncology ( Site 4001)Recruiting
- Northern Hospital-Department of Medical Oncology ( Site 4003)Recruiting
- Cabrini Hospital - Malvern-Cabrini Institute ( Site 4000)Recruiting
- Antwerp University Hospital-Oncology ( Site 1002)Recruiting
- Cliniques universitaires Saint-Luc-Medical Oncology ( Site 1001)Recruiting
- Université Catholique de Louvain-Namur - Centre Hospitalier -Oncology ( Site 1003)Recruiting
- UZ Leuven ( Site 1000)Recruiting
- Centro Investigación del Cáncer James Lind ( Site 3107)Recruiting
- Clínica Puerto Montt ( Site 3110)Recruiting
- FALP-UIDO ( Site 3102)Recruiting
- Oncovida ( Site 3108)Recruiting
- Bradfordhill-Clinical Area ( Site 3100)Recruiting
- Centre Eugène Marquis Rennes - Centre de Lutte Contre le Cancer ( Site 1103)Recruiting
- CHU Besançon-Medical oncology ( Site 1101)Recruiting
- Institut Régional du Cancer Montpellier ( Site 1106)Recruiting
- Hôpital Beaujon-Oncologie Digestive ( Site 1104)Recruiting
- Centre Hospitalier Universitaire de Grenoble-Medical Oncology ( Site 1105)Recruiting
- Rambam Health Care Campus-Oncology ( Site 1300)Recruiting
- Hadassah Medical Center-Oncology ( Site 1303)Recruiting
- Sheba Medical Center-ONCOLOGY ( Site 1302)Recruiting
- Sourasky Medical Center-Oncology ( Site 1301)Recruiting
- Seoul National University Hospital-Internal Medicine ( Site 4103)Recruiting
- Severance Hospital, Yonsei University Health System-Medical oncology ( Site 4100)Recruiting
- Asan Medical Center-Department of Oncology ( Site 4101)Recruiting
- Samsung Medical Center-Division of Hematology/Oncology ( Site 4102)Recruiting
- Maastricht UMC+-Medical Oncology ( Site 1501)Recruiting
- Leids Universitair Medisch Centrum-Medical Oncology ( Site 1504)Recruiting
- Universitair Medisch Centrum Utrecht-Medical Oncology ( Site 1503)Recruiting
- Auckland City Hospital-Liver Research Unit ( Site 4201)Recruiting
- Auckland City Hospital-Cancer & Blood Research ( Site 4200)Recruiting
- Hospital Universitario Central de Asturias-Medical Oncology ( Site 1802)Recruiting
- CHUS - Hospital Clinico Universitario-Servicio de Oncologia ( Site 1807)Recruiting
- HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1801)Recruiting
- Hospital Universitari Vall d'Hebron-Oncology ( Site 1800)Recruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm 1: Pembrolizumab + Belzutifan + Lenvatinib
Arm 2: Pembrolizumab + Lenvatinib
Participants will receive pembrolizumab 400 mg PLUS belzutifan 120 mg PLUS lenvatinib 20 mg (For HCC: 8 mg [body weight <60kg] or 12 mg [body weight ≥ 60 kg]). Pembrolizumab will be administered via intravenous (IV) infusion once every 6 weeks (Q6W) for a maximum of 18 doses (approximately 2 years). Belzutifan and lenvatinib will be administered orally once daily (QD) until progressive disease or discontinuation.
Participants with IO resistant ESCC will receive pembrolizumab 400 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered via intravenous (IV) infusion once every 6 weeks (Q6W) for a maximum of 18 doses (approximately 2 years). Lenvatinib will be administered orally once daily (QD) until progressive disease or discontinuation.