Solid tumors
Conditions
Interventions
All cohorts will receive: Q6W 400mg Pembrolizumab, daily 20mg Lenvatinib (for
HCC, 8mg if 60kg) and daily 120mg Belzutifan.
Sponsors
Merck Sharp & Dohme (MSD)
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Diagnosis of one of the following advanced (unresectable and/or metastatic) solid tumors, documented by histopathology or cytopathology: - HCC - CRC - PDAC - BTC - ESCC 2. Disease progression on or since the most recent treatment (does not applicable to newly diagnosed unresectable or metastatic HCC). 3. Measurable disease per RECIST v1.1 as assessed locally (by investigator) and verified by BICR. 4. Submission of an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. 5. Male or female, at least 18 years of age. 6. Male participants are abstinent from heterosecual intercourse or agree to follow contraceptive guidance during and for at least 7 days after last dose of study intervention with belzutifan and lenvatinib. 7. Female participants are not pregnant or breastfeeding, not a woman of child-baering potential (WOCBP) or is a WOCBP and agrees to follow contraceptive guidance during the intervention period 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 after the last dose of study intervention. 8. ECOG performance status of 0 to 1 within 7 days of before the start of study intervention. 9. Adequate organ function 10. Adequately controlled blood pressure with or without antihypertensive medications. Additional specific inclusion criteria are applicable per cohort, please refer to the protocol
Exclusion criteria
Exclusion criteria: 1. Unable to swallow orally administered medication or has a significant GI disorder that may affect study intervention absorption. 2. History of a second malignancy that is progressing or has required active treatment within 3 years. 3. A pulse oximeter reading 480 ms. 7. Urine protein >=1 g/24 hours. 8. Symptomatic pleural effusion unless clinically stable after treatment. 9. Preexisting >= Grade 3 GI or non-GI fistula. 10. Moderate to severe hepatic impairment (Child-Pugh B or C). 11. Clinically significant history of bleeding within 3 months before screening. 12. Presence of serious active nonhealing wound/ulcer/bone fracture 13. Requirement for hemodialysis or peritoneal dialysis 14. Received colony-stimulating factors or transfusion within 28 days before study treatment initiation. For the complete list, please refer to the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary outcome to asses safety and tolerability - Dose-limiting toxicity (DLTs) (Safety Lead-in Phase only). - Adverse events (AEs). - Study intervention discontinuations due to AEs. Primary outcome to evaluate ORR - Objective response (OR): complete response (CR) or partial response (PR) | — |
Secondary
| Measure | Time frame |
|---|---|
| - DOR: the time from first documented evidence of CR or PR until either disease progression or death due to any cause, whichever occurs first. - Disease control (DC): best overall response of CR, PR, or stable disease (SD) after >=6 weeks (the start of the window for the first scheduled scan). - PFS: the time from first day of study intervention to the first documented disease progression or death due to any cause, whichever occurs first. - OS: the time from first day of study intervention to death due to any cause. - OR, DOR, DC, and PFS | — |
Countries
Netherlands
Outcome results
None listed