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

NCT ID: NCT04976634

Last Updated: 2025-04-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

730 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-18

Study Completion Date

2027-03-22

Brief Summary

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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.

Detailed Description

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Effective as of Amendment 3 (26 Mar 2025), enrollment of participants with ESCC will be closed.

Conditions

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Neoplasm Malignant

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1: Pembrolizumab + Belzutifan + 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.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type DRUG

Pembrolizumab 400 mg administered Q6W via IV infusion

Belzutifan

Intervention Type DRUG

Belzutifan 120 mg administered QD via oral tablet

Lenvatinib

Intervention Type DRUG

Lenvantinib dose for HCC is 8 mg QD for body weight \<60 kg and 12 mg QD for body weight ≥ 60 kg administered via oral capsule. For all other tumors, the lenvatinib dose is 20 mg QD administered via oral capsule

Arm 2: Pembrolizumab + Lenvatinib

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.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type DRUG

Pembrolizumab 400 mg administered Q6W via IV infusion

Lenvatinib

Intervention Type DRUG

Lenvantinib dose for HCC is 8 mg QD for body weight \<60 kg and 12 mg QD for body weight ≥ 60 kg administered via oral capsule. For all other tumors, the lenvatinib dose is 20 mg QD administered via oral capsule

Interventions

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Pembrolizumab

Pembrolizumab 400 mg administered Q6W via IV infusion

Intervention Type DRUG

Belzutifan

Belzutifan 120 mg administered QD via oral tablet

Intervention Type DRUG

Lenvatinib

Lenvantinib dose for HCC is 8 mg QD for body weight \<60 kg and 12 mg QD for body weight ≥ 60 kg administered via oral capsule. For all other tumors, the lenvatinib dose is 20 mg QD administered via oral capsule

Intervention Type DRUG

Other Intervention Names

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MK-3475 KEYTRUDA® MK-6482 PT2977 WELIREG™ MK-7902 E7080 LENVIMA®

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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University of Arizona Cancer Center-University of Arizona Cancer Center - North Campus ( Site 5047)

Tucson, Arizona, United States

Site Status

City of Hope Comprehensive Cancer Center ( Site 5002)

Duarte, California, United States

Site Status

Cedars-Sinai Medical Center ( Site 5045)

Los Angeles, California, United States

Site Status

UCSF Medical Center at Mission Bay ( Site 5021)

San Francisco, California, United States

Site Status

Yale-New Haven Hospital-Yale Cancer Center ( Site 5013)

New Haven, Connecticut, United States

Site Status

Sibley Memorial Hospital ( Site 5051)

Washington D.C., District of Columbia, United States

Site Status

University of Florida College of Medicine ( Site 5015)

Gainesville, Florida, United States

Site Status

Johns Hopkins Hospital-Sidney Kimmel Comprehensive Cancer Center - GI and Immunology ( Site 5048)

Baltimore, Maryland, United States

Site Status

Brigitte Harris Cancer Pavilion ( Site 5055)

Detroit, Michigan, United States

Site Status

Memorial Sloan Kettering Cancer Center ( Site 5050)

New York, New York, United States

Site Status

Duke Cancer Institute ( Site 5026)

Durham, North Carolina, United States

Site Status

University of Texas MD Anderson Cancer Center-Gastrointestinal Medical Oncology ( Site 5049)

Houston, Texas, United States

Site Status

Inova Schar Cancer Institute ( Site 5039)

Fairfax, Virginia, United States

Site Status

Blue Ridge Cancer Care ( Site 5053)

Roanoke, Virginia, United States

Site Status

Northwest Medical Specialties, PLLC ( Site 5025)

Tacoma, Washington, United States

Site Status

University of Wisconsin Hospitals and Clinics ( Site 5037)

Madison, Wisconsin, United States

Site Status

Gosford Hospital-Oncology Trials ( Site 4004)

Gosford, New South Wales, Australia

Site Status

Westmead Hospital-Department of Medical Oncology ( Site 4001)

Westmead, New South Wales, Australia

Site Status

Northern Hospital-Department of Medical Oncology ( Site 4003)

Epping, Victoria, Australia

Site Status

Cabrini Hospital - Malvern-Cabrini Institute ( Site 4000)

Malvern, Victoria, Australia

Site Status

Antwerp University Hospital-Oncology ( Site 1002)

Edegem, Antwerpen, Belgium

Site Status

Cliniques universitaires Saint-Luc-Medical Oncology ( Site 1001)

Brussels, Bruxelles-Capitale, Region de, Belgium

Site Status

UZ Leuven ( Site 1000)

Leuven, Vlaams-Brabant, Belgium

Site Status

AZ Delta vzw ( Site 1004)

Roeselare, West-Vlaanderen, Belgium

Site Status

Université Catholique de Louvain-Namur - Centre Hospitalier -Oncology ( Site 1003)

Namur, , Belgium

Site Status

Clínica Puerto Montt ( Site 3110)

Port Montt, Los Lagos Region, Chile

Site Status

FALP-UIDO ( Site 3102)

Santiago, Region M. de Santiago, Chile

Site Status

Oncovida ( Site 3108)

Santiago, Region M. de Santiago, Chile

Site Status

Bradfordhill-Clinical Area ( Site 3100)

Santiago, Region M. de Santiago, Chile

Site Status

Centro Investigación del Cáncer James Lind ( Site 3107)

Temuco, Región de la Araucanía, Chile

Site Status

Centre Eugène Marquis Rennes - Centre de Lutte Contre le Cancer ( Site 1103)

Rennes, Brittany Region, France

Site Status

CHU Besançon-Medical oncology ( Site 1101)

Besançon, Doubs, France

Site Status

CHU Brest Cavale Blanche ( Site 1107)

Brest, Finistere, France

Site Status

Institut Regional du Cancer Montpellier ( Site 1106)

Montpellier, Herault, France

Site Status

Centre Hospitalier Universitaire de Grenoble-Medical Oncology ( Site 1105)

La Tronche, Isere, France

Site Status

Sainte Catherine Institut du Cancer Avignon Provence ( Site 1108)

Avignon, Vaucluse, France

Site Status

Hôpital Beaujon-Oncologie Digestive ( Site 1104)

Clichy, Île-de-France Region, France

Site Status

Rambam Health Care Campus-Oncology ( Site 1300)

Haifa, , Israel

Site Status

Hadassah Medical Center-Oncology ( Site 1303)

Jerusalem, , Israel

Site Status

Sheba Medical Center-ONCOLOGY ( Site 1302)

Ramat Gan, , Israel

Site Status

Sourasky Medical Center-Oncology ( Site 1301)

Tel Aviv, , Israel

Site Status

Maastricht UMC+-Medical Oncology ( Site 1501)

Maastricht, Limburg, Netherlands

Site Status

Leids Universitair Medisch Centrum-Medical Oncology ( Site 1504)

Leiden, South Holland, Netherlands

Site Status

Universitair Medisch Centrum Utrecht-Medical Oncology ( Site 1503)

Utrecht, , Netherlands

Site Status

Auckland City Hospital-Liver Research Unit ( Site 4201)

Grafton, Auckland, New Zealand

Site Status

Auckland City Hospital-Cancer & Blood Research ( Site 4200)

Auckland, , New Zealand

Site Status

Chonnam National University Hwasun Hospital-Hemato-Oncology ( Site 4105)

Hwasun Gun, Jeonranamdo, South Korea

Site Status

Keimyung University Dongsan Hospital CRC room 1 ( Site 4104)

Daegu, Taegu-Kwangyokshi, South Korea

Site Status

Seoul National University Hospital-Internal Medicine ( Site 4103)

Seoul, , South Korea

Site Status

Severance Hospital, Yonsei University Health System-Medical oncology ( Site 4100)

Seoul, , South Korea

Site Status

Asan Medical Center-Department of Oncology ( Site 4101)

Seoul, , South Korea

Site Status

Samsung Medical Center-Division of Hematology/Oncology ( Site 4102)

Seoul, , South Korea

Site Status

Hospital Germans Trias i Pujol-Instituto Catalán de Oncología de Badalona ( Site 1806)

Badalona, Barcelona, Spain

Site Status

CHUS - Hospital Clinico Universitario-Servicio de Oncologia ( Site 1807)

Santiago de Compostela, La Coruna, Spain

Site Status

HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1801)

Madrid, Madrid, Comunidad de, Spain

Site Status

Hospital Universitario Central de Asturias-Medical Oncology ( Site 1802)

Oviedo, Principality of Asturias, Spain

Site Status

Hospital Universitari Vall d'Hebron-Oncology ( Site 1800)

Barcelona, , Spain

Site Status

Countries

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United States Australia Belgium Chile France Israel Netherlands New Zealand South Korea Spain

References

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Gebrael G, Sahu KK, Agarwal N, Maughan BL. Update on combined immunotherapy for the treatment of advanced renal cell carcinoma. Hum Vaccin Immunother. 2023 Dec 31;19(1):2193528. doi: 10.1080/21645515.2023.2193528. Epub 2023 Apr 16.

Reference Type DERIVED
PMID: 37062953 (View on PubMed)

Related Links

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Other Identifiers

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MK-6482-016

Identifier Type: OTHER

Identifier Source: secondary_id

2023-503905-12-00

Identifier Type: CTIS

Identifier Source: secondary_id

U1111-1288-3020

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-005007-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

6482-016

Identifier Type: -

Identifier Source: org_study_id

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