Pembrolizumab Plus Lenvatinib in Combination With MK-6482 in Multiple Solid Tumors

What is the Purpose of this Study?

The purpose of this study is to evaluate the combined use of the drugs pembrolizumab (pembro), lenvatinib, and belzutifan in people with certain types of solid tumors. Pembro and lenvatinib have been approved by the U.S. Food and Drug Administration (FDA) to treat many cancer types. Belzutifan (MK-6482) is FDA-approved to treat adults with various diseases but has not been approved for the conditions being examined in this study. The study focuses on individuals who have solid tumors from cancer of the liver, colon, pancreas, bile duct, or gall bladder. All participants will receive the combination of pembro, lenvatinib and belzutifan. Pembro will be given by a needle in a vein once every 6 weeks for up to 2 years. Lenvatinib will be given as capsules taken by mouth once a day; belzutifan will be given as tablets taken by mouth once a day.

Eligibility

* 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 \[dMMR\])

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

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Where can I participate?

CS Cancer at Beverly Hills
CS Cancer at Cedars-Sinai Medical Center

More about this Clinical Trial

What is the full name of this clinical trial?

MK-6482-016: 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

Study Details

Disease Type/Condition

Gastrointestinal Cancer, Liver Cancer

Principal Investigator

Gong, Jun

Co-Investigators

Andrew Hendifar, Arsen Osipov, David Hoffman, Emily Kaymen, Jeremy Lorber, Kamya Sankar

Age Group

Adult

Phase

IRB Number

STUDY00001633

ClinicalTrials.gov ID

NCT04976634

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org