Pembrolizumab Plus Lenvatinib in Combination With Belzutifan in Solid Tumors (MK-6482-016)

Running, not enrolling · Phase 2

Conditions studied: Neoplasm Malignant

In brief

The purpose of this study is to determine the safety and efficacy of belzutifan in combination with pembrolizumab and lenvatinib in multiple solid tumors including hepatocellular carcinoma (HCC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), biliary tract cancer (BTC), endometrial cancer (EC),and esophageal squamous cell carcinoma (ESCC). There is no formal hypothesis testing in this study.

Key facts

Study ID

NCT04976634

Run by

Merck Sharp & Dohme LLC

People needed

730

Starts

2021-08-18

Expected to finish

2027-03-22

Last updated by the study team

2025-04-06

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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)

You may not qualify if…

• 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

Where it is running

• City of Hope Comprehensive Cancer Center ( Site 5002) — Duarte, California, United States
• Cedars-Sinai Medical Center ( Site 5045) — Los Angeles, California, United States
• UCSF Medical Center at Mission Bay ( Site 5021) — San Francisco, California, United States
• Yale-New Haven Hospital-Yale Cancer Center ( Site 5013) — New Haven, Connecticut, United States
• Sibley Memorial Hospital ( Site 5051) — Washington D.C., District of Columbia, United States
• University of Florida College of Medicine ( Site 5015) — Gainesville, Florida, United States
• Johns Hopkins Hospital-Sidney Kimmel Comprehensive Cancer Center - GI and Immunology ( Site 5048) — Baltimore, Maryland, United States
• Brigitte Harris Cancer Pavilion ( Site 5055) — Detroit, Michigan, United States
• Memorial Sloan Kettering Cancer Center ( Site 5050) — New York, New York, United States
• Duke Cancer Institute ( Site 5026) — Durham, North Carolina, United States
• University of Texas MD Anderson Cancer Center-Gastrointestinal Medical Oncology ( Site 5049) — Houston, Texas, United States
• Inova Schar Cancer Institute ( Site 5039) — Fairfax, Virginia, United States
• Blue Ridge Cancer Care ( Site 5053) — Roanoke, Virginia, United States
• Northwest Medical Specialties, PLLC ( Site 5025) — Tacoma, Washington, United States
• University of Wisconsin Hospitals and Clinics ( Site 5037) — Madison, Wisconsin, United States
• Gosford Hospital-Oncology Trials ( Site 4004) — Gosford, New South Wales, Australia
• Westmead Hospital-Department of Medical Oncology ( Site 4001) — Westmead, New South Wales, Australia
• Northern Hospital-Department of Medical Oncology ( Site 4003) — Epping, Victoria, Australia
• Cabrini Hospital - Malvern-Cabrini Institute ( Site 4000) — Malvern, Victoria, Australia
• Antwerp University Hospital-Oncology ( Site 1002) — Edegem, Antwerpen, Belgium
• Cliniques universitaires Saint-Luc-Medical Oncology ( Site 1001) — Brussels, Bruxelles-Capitale, Region de, Belgium
• UZ Leuven ( Site 1000) — Leuven, Vlaams-Brabant, Belgium
• AZ Delta vzw ( Site 1004) — Roeselare, West-Vlaanderen, Belgium
• Université Catholique de Louvain-Namur - Centre Hospitalier -Oncology ( Site 1003) — Namur, Belgium
• University of Arizona Cancer Center-University of Arizona Cancer Center - North Campus ( Site 5047) — Tucson, Arizona, United States

Full record on ClinicalTrials.gov

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