An Open-label, Multicenter, Phase 2 Study to Evaluate the Efficacy and Safety of Pembrolizumab Plus Lenvatinib in Combination With Belzutifan in Multiple Solid Tumors

  • End date
    Aug 18, 2026
  • participants needed
  • sponsor
    Merck Sharp & Dohme LLC
Updated on 15 October 2022
measurable disease
squamous cell carcinoma


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.

Condition Carcinoma, Hepatocellular, Colorectal Neoplasms, Pancreatic Ductal Adenocarcinoma, Biliary Tract Neoplasms, Endometrial Neoplasms, Esophageal Neoplasms
Treatment Pembrolizumab, Lenvatinib, Belzutifan
Clinical Study IdentifierNCT04976634
SponsorMerck Sharp & Dohme LLC
Last Modified on15 October 2022


Yes No Not Sure

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)
Disease progression on or since the most recent treatment (does not apply to newly
Esophageal squamous cell carcinoma (ESCC)
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
diagnosed unresectable or metastatic HCC or EC)
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)
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
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
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
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
A pulse oximeter reading <92% at rest, or requirement of intermittent supplemental oxygen/ chronic supplemental oxygen
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
Preexisting ≥ Grade 3 gastrointestinal (GI) or non-GI fistula
History of Hepatitis B or active Hepatis C virus infections. with exceptions for HCC and BTC
Radiographic evidence of intratumoral cavitation, or invasion/infiltration of a major blood vessel
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)
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
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