Study of Favezelimab Coformulated With Pembrolizumab (MK-4280A) in Participants With Selected Solid Tumors (MK-4280A-010)

NCT ID: NCT06036836

Last Updated: 2025-12-18

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

160 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-29

Study Completion Date

2026-03-31

Brief Summary

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The purpose of this study is to evaluate pathologic complete response (pCR) rate of coformulated favezelimab/pembrolizumab (MK-4280A) or pembrolizumab as assessed by blinded central pathology review (BICR) in participants with cutaneous squamous cell carcinoma (cSCC) \[Cohort A\] and to evaluate lenvatinib in combination with coformulated favezelimab/pembrolizumab or pembrolizumab with respect to objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by investigator in participants proficient in mismatch repair (pMMR) endometrial cancer (EC) \[Cohort B\].

Detailed Description

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Conditions

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Solid Tumor Cutaneous Squamous Cell Carcinoma Endometrial Cancer

Keywords

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Programmed Cell Death-1 (PD1, PD-1) Programmed Cell Death-2 (PD2, PD-2) Programmed Cell Death Receptor Ligand 1 (PDL1, PD-L1) Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2) Lymphocyte-Activation Gene 3 (LAG-3)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Favezelimab/Pembrolizumab

Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) via an intravenous (IV) infusion every 3 weeks (Q3W) for 3 cycles in the neoadjuvant period and 14 cycles of adjuvant therapy. Each cycle is 21 days. Participants who do not complete all 3 neoadjuvant cycles should have additional cycles in the adjuvant period so that the total number of study intervention administrations is 17 treatment cycles.

Group Type EXPERIMENTAL

favezelimab/pembrolizumab

Intervention Type BIOLOGICAL

IV infusion

Pembrolizumab

Participants will receive 200 mg pembrolizumab via an IV infusion Q3W for 3 cycles in the neoadjuvant period and 14 cycles of adjuvant therapy. Each cycle is 21 days. Participants who do not complete all 3 neoadjuvant cycles should have additional cycles in the adjuvant period so that the total number of study intervention administrations is 17 treatment cycles.

Group Type EXPERIMENTAL

pembrolizumab

Intervention Type BIOLOGICAL

IV infusion

Favezelimab/Pembrolizumab + Lenvatinib (Cohort B)

Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) via IV infusion Q3W for up to 35 cycles (each cycle is 21 days) PLUS lenvatinib every day (QD) 20 mg orally until disease progression, unacceptable toxicity, or discontinuation criteria are met.

Group Type EXPERIMENTAL

favezelimab/pembrolizumab

Intervention Type BIOLOGICAL

IV infusion

lenvatinib

Intervention Type DRUG

Oral administration of capsule

Pembrolizumab + Lenvatinib (Cohort B)

Participants will receive 200 mg pembrolizumab via IV infusion Q3W for up to 35 cycles (each cycle is 21 days) PLUS lenvatinib QD 20 mg orally until disease progression, unacceptable toxicity, or discontinuation criteria are met.

Group Type EXPERIMENTAL

pembrolizumab

Intervention Type BIOLOGICAL

IV infusion

lenvatinib

Intervention Type DRUG

Oral administration of capsule

Interventions

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favezelimab/pembrolizumab

IV infusion

Intervention Type BIOLOGICAL

pembrolizumab

IV infusion

Intervention Type BIOLOGICAL

lenvatinib

Oral administration of capsule

Intervention Type DRUG

Other Intervention Names

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MK-4280A MK-3475 Keytruda®

Eligibility Criteria

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Inclusion Criteria

Cohort A only

* Histologically confirmed diagnosis of resectable cutaneous squamous cell carcinoma (cSCC) as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary cancer is not permitted)
* Stage II to Stage IV disease without distant metastasis (M1). cSCC tumors arising in the head and neck will be staged according to American Joint Committee on Cancer (AJCC) Edition (Ed.) 8 and cSCC tumors arising in non-head and neck locations will be staged according to Union for International Cancer Control (UICC) Ed. 8
* Is systemic treatment naïve
* Archival tumor tissue sample, or newly obtained surgical resection, or biopsy sample of a tumor lesion not previously irradiated has been provided
* Is an individual of any sex/gender, at least 18 years of age at the time of providing the informed consent

Cohort B only

* Histologically confirmed diagnosis of endometrial cancer (EC) that is not deficient in mismatch repair (dMMR) proficient in mismatch repair (pMMR) as documented by a local test report
* Documented evidence of stage IVB (per 2009 International Federation of Gynecology and Obstetrics (FIGO) staging), recurrent, or metastatic EC, and are not candidates for curative surgery or radiation
* Has radiographic evidence of disease progression after 1 prior systemic, platinum-based chemotherapy regimen for EC in any setting
* Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST 1.1) by investigator (before first dose of study intervention)
* Is assigned female sex at birth, at least 18 years of age at the time of providing the informed consent
* Has adequately controlled blood pressure without antihypertensive medication

All Cohorts

* Agrees to follow contraception guidelines if a participant of childbearing potential
* Has a life expectancy \>3 years per investigator assessment
* Has adequate organ function
* Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* If positive for hepatitis B, has received antiviral therapy for ≥4 weeks and undetectable viral load prior to randomization
* If positive for hepatitis C, has undetectable viral load at screening
* If positive for human immunodeficiency virus (HIV), has well-controlled HIV on a stable highly active antiretroviral therapy

Exclusion Criteria

All Cohorts

* Has known hypersensitivity to active substances or their excipients including previous clinically significant hypersensitivity reaction to treatment with other monoclonal antibody (mAb)
* History of allogeneic tissue/solid organ transplant

Cohort A only

* Received prior radiotherapy to the index lesion (in-field lesion)
* Participants for whom the primary site of cSCC was anogenital area (penis, scrotum, vulva, perianal region) are not eligible

Cohort B

* Has had major surgery within 3 weeks prior to first dose of study interventions
* Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula
* Has urine protein ≥1 g/24 hours
* Has a left ventricle ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multi-gated acquisition (MUGA) or echocardiogram (ECHO)
* Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
* Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
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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Yale-New Haven Hospital-Yale Cancer Center ( Site 0643)

New Haven, Connecticut, United States

Site Status

Dana-Farber Cancer Institute ( Site 0642)

Boston, Massachusetts, United States

Site Status

Rutgers Cancer Institute of New Jersey ( Site 0635)

New Brunswick, New Jersey, United States

Site Status

Duke Cancer Institute ( Site 0641)

Durham, North Carolina, United States

Site Status

Cleveland Clinic Main ( Site 0639)

Cleveland, Ohio, United States

Site Status

St. Luke's University Health Network ( Site 0636)

Bethlehem, Pennsylvania, United States

Site Status

UPMC Hillman Cancer Center ( Site 0644)

Pittsburgh, Pennsylvania, United States

Site Status

UT Southwestern Medical Center-CRO-Simmons Comprehensive Cancer Center ( Site 0645)

Dallas, Texas, United States

Site Status

St Vincent's Hospital-The Kinghorn Cancer Centre ( Site 0005)

Darlinghurst, New South Wales, Australia

Site Status

Royal North Shore Hospital ( Site 0008)

St Leonards, New South Wales, Australia

Site Status

Blacktown Hospital ( Site 0003)

Sydney, New South Wales, Australia

Site Status

Royal Brisbane and Women's Hospital ( Site 0002)

Brisbane, Queensland, Australia

Site Status

The Alfred Hospital ( Site 0004)

Melbourne, Victoria, Australia

Site Status

Fiona Stanley Hospital ( Site 0006)

Murdock, Western Australia, Australia

Site Status

Sunnybrook Research Institute ( Site 0607)

Toronto, Ontario, Canada

Site Status

Princess Margaret Cancer Centre ( Site 0606)

Toronto, Ontario, Canada

Site Status

Centre Hospitalier de l'Université de Montréal ( Site 0602)

Montreal, Quebec, Canada

Site Status

Jewish General Hospital ( Site 0605)

Montreal, Quebec, Canada

Site Status

McGill University Health Centre ( Site 0604)

Montreal, Quebec, Canada

Site Status

Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0

Québec, Quebec, Canada

Site Status

Institut de cancérologie Strasbourg Europe (ICANS) ( Site 0153)

Strasbourg, Alsace, France

Site Status

CENTRE LEON BERARD ( Site 0151)

Lyon Cedex08, Auvergne-Rhône-Alpes, France

Site Status

Centre Hospitalier Régional Universitaire de Brest - Hôpital Morvan ( Site 0154)

Brest, Finistere, France

Site Status

Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 0155)

Paris, , France

Site Status

Universitaetsklinikum Essen ( Site 0185)

Essen, North Rhine-Westphalia, Germany

Site Status

Universitaetsklinikum Essen-Klinik für Dermatologie, Venerologie und Allergologie ( Site 0182)

Essen, North Rhine-Westphalia, Germany

Site Status

Universitaetsklinikum Carl Gustav Carus Dresden-Klinik und Poliklinik für Dermatologie ( Site 0183)

Dresden, Saxony, Germany

Site Status

Fondazione IRCCS Istituto Nazionale dei Tumori-SC Oncologia Medica 3 - Tumori Testa-collo ( Site 025

Milan, Lombardy, Italy

Site Status

Istituto Nazionale Tumori IRCCS Fondazione Pascale-s.c. melanoma, immunoterapia oncologica e terapi

Napoli, , Italy

Site Status

Hospital Sultan Ismail-Pusat Rawatan Radioterapi Dan Onkologi ( Site 0063)

Johor Bahru, Johor, Malaysia

Site Status

University Malaya Medical Centre ( Site 0061)

Lembah Pantai, Kuala Lumpur, Malaysia

Site Status

Sarawak General Hospital-Radiotherapy Unit ( Site 0062)

Kuching, Sarawak, Malaysia

Site Status

Radboudumc ( Site 0274)

Nijmegen, Gelderland, Netherlands

Site Status

Erasmus Medisch Centrum ( Site 0272)

Rotterdam, South Holland, Netherlands

Site Status

University Medical Center Groningen ( Site 0273)

Groningen, , Netherlands

Site Status

Taichung Veterans General Hospital-GYNECOLOGY ( Site 0033)

Taichung, , Taiwan

Site Status

National Cheng Kung University Hospital-Clinical Trial Center ( Site 0032)

Tainan, , Taiwan

Site Status

National Taiwan University Hospital ( Site 0031)

Taipei, , Taiwan

Site Status

Medipol Mega Universite Hastanesi-oncology ( Site 0425)

Stanbul, Istanbul, Turkey (Türkiye)

Site Status

Gulhane Egitim Arastirma Hastanesi-Onkoloji ( Site 0424)

Ankara, , Turkey (Türkiye)

Site Status

Hacettepe Universite Hastaneleri-oncology hospital ( Site 0421)

Ankara, , Turkey (Türkiye)

Site Status

Liv Hospital Ankara-Oncology ( Site 0426)

Ankara, , Turkey (Türkiye)

Site Status

Ankara Bilkent Şehir Hastanesi ( Site 0427)

Ankara, , Turkey (Türkiye)

Site Status

TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 0423)

Istanbul, , Turkey (Türkiye)

Site Status

Countries

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United States Australia Canada France Germany Italy Malaysia Netherlands Taiwan Turkey (Türkiye)

Related Links

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Other Identifiers

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MK-4280A-010

Identifier Type: OTHER

Identifier Source: secondary_id

2023-505022-34-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1290-7288

Identifier Type: REGISTRY

Identifier Source: secondary_id

4280A-010

Identifier Type: -

Identifier Source: org_study_id