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ACTIVE NOT RECRUITING

NCT04976634

PHASE2

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

Sponsor: Merck Sharp & Dohme LLC

View on ClinicalTrials.gov

Summary

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.

Official title: 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

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

730

Start Date

2021-08-18

Completion Date

2027-03-22

Last Updated

2025-04-06

Healthy Volunteers

Conditions

Neoplasm Malignant

Interventions

DRUG

Pembrolizumab

Pembrolizumab 400 mg administered Q6W via IV infusion

DRUG

Belzutifan

Belzutifan 120 mg administered QD via oral tablet

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

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

Locations (57)

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

Tucson, Arizona, United States

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

Clínica Puerto Montt ( Site 3110)

Port Montt, Los Lagos Region, Chile

FALP-UIDO ( Site 3102)

Santiago, Region M. de Santiago, Chile

Oncovida ( Site 3108)

Santiago, Region M. de Santiago, Chile

Bradfordhill-Clinical Area ( Site 3100)

Santiago, Region M. de Santiago, Chile

Centro Investigación del Cáncer James Lind ( Site 3107)

Temuco, Región de la Araucanía, Chile

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

Rennes, Brittany Region, France

CHU Besançon-Medical oncology ( Site 1101)

Besançon, Doubs, France

CHU Brest Cavale Blanche ( Site 1107)

Brest, Finistere, France

Institut Regional du Cancer Montpellier ( Site 1106)

Montpellier, Herault, France

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

La Tronche, Isere, France

Sainte Catherine Institut du Cancer Avignon Provence ( Site 1108)

Avignon, Vaucluse, France

Hôpital Beaujon-Oncologie Digestive ( Site 1104)

Clichy, Île-de-France Region, France

Rambam Health Care Campus-Oncology ( Site 1300)

Haifa, Israel

Hadassah Medical Center-Oncology ( Site 1303)

Jerusalem, Israel

Sheba Medical Center-ONCOLOGY ( Site 1302)

Ramat Gan, Israel

Sourasky Medical Center-Oncology ( Site 1301)

Tel Aviv, Israel

Maastricht UMC+-Medical Oncology ( Site 1501)

Maastricht, Limburg, Netherlands

Leids Universitair Medisch Centrum-Medical Oncology ( Site 1504)

Leiden, South Holland, Netherlands

Universitair Medisch Centrum Utrecht-Medical Oncology ( Site 1503)

Utrecht, Netherlands

Auckland City Hospital-Liver Research Unit ( Site 4201)

Grafton, Auckland, New Zealand

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

Auckland, New Zealand

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

Hwasun Gun, Jeonranamdo, South Korea

Keimyung University Dongsan Hospital CRC room 1 ( Site 4104)

Daegu, Taegu-Kwangyokshi, South Korea

Seoul National University Hospital-Internal Medicine ( Site 4103)

Seoul, South Korea

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

Seoul, South Korea

Asan Medical Center-Department of Oncology ( Site 4101)

Seoul, South Korea

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

Seoul, South Korea

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

Badalona, Barcelona, Spain

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

Santiago de Compostela, La Coruna, Spain

HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1801)

Madrid, Madrid, Comunidad de, Spain

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

Oviedo, Principality of Asturias, Spain

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

Barcelona, Spain

Clinical Research Directory

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

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (57)