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

A Multicenter, Randomized, Double-Blind, Phase 2, Basket Study of MK-4280A, a Coformulation of Favezelimab (MK-4280) With Pembrolizumab (MK-3475) in Selected Solid Tumors (KeyForm-010)

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].

Study Overview

• Status: Completed
• Conditions: Solid Tumor; Endometrial Cancer; Cutaneous Squamous Cell Carcinoma
• Intervention / Treatment: Biological: pembrolizumab; Biological: favezelimab/pembrolizumab; Drug: lenvatinib

• Study Type: Interventional
• Enrollment (Actual): 163
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital-The Kinghorn Cancer Centre ( Site 0005)
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital ( Site 0008)
    • Sydney, New South Wales, Australia, 2148
      • Blacktown Hospital ( Site 0003)
  • Queensland
    • Brisbane, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital ( Site 0002)
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital ( Site 0004)
  • Western Australia
    • Murdock, Western Australia, Australia, 6150
      • Fiona Stanley Hospital ( Site 0006)
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Research Institute ( Site 0607)
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre ( Site 0606)
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital ( Site 0605)
    • Montreal, Quebec, Canada, H2X 3E4
      • Centre Hospitalier de l'Université de Montréal ( Site 0602)
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre ( Site 0604)
    • Québec, Quebec, Canada, G1J 1Z4
      • Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0
• France
  • Paris, France, 75014
    • Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 0155)
  • Alsace
    • Strasbourg, Alsace, France, 67200
      • Institut de cancérologie Strasbourg Europe (ICANS) ( Site 0153)
  • Auvergne-Rhône-Alpes
    • Lyon Cedex08, Auvergne-Rhône-Alpes, France, 69373
      • CENTRE LEON BERARD ( Site 0151)
  • Finistere
    • Brest, Finistere, France, 29200
      • Centre Hospitalier Régional Universitaire de Brest - Hôpital Morvan ( Site 0154)
• Germany
  • North Rhine-Westphalia
    • Essen, North Rhine-Westphalia, Germany, 45147
      • Universitaetsklinikum Essen ( Site 0185)
    • Essen, North Rhine-Westphalia, Germany, 45147
      • Universitaetsklinikum Essen-Klinik für Dermatologie, Venerologie und Allergologie ( Site 0182)
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Universitaetsklinikum Carl Gustav Carus Dresden-Klinik und Poliklinik für Dermatologie ( Site 0183)
• Italy
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori IRCCS Fondazione Pascale-s.c. melanoma, immunoterapia oncologica e terapi
  • Lombardy
    • Milan, Lombardy, Italy, 20133
      • Fondazione IRCCS Istituto Nazionale dei Tumori-SC Oncologia Medica 3 - Tumori Testa-collo ( Site 025
• Malaysia
  • Johor
    • Johor Bahru, Johor, Malaysia, 81100
      • Hospital Sultan Ismail-Pusat Rawatan Radioterapi Dan Onkologi ( Site 0063)
  • Kuala Lumpur
    • Lembah Pantai, Kuala Lumpur, Malaysia, 59100
      • University Malaya Medical Centre ( Site 0061)
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Sarawak General Hospital-Radiotherapy Unit ( Site 0062)
• Netherlands
  • Groningen, Netherlands, 9713GZ
    • University Medical Center Groningen ( Site 0273)
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Radboudumc ( Site 0274)
  • South Holland
    • Rotterdam, South Holland, Netherlands, 3015 GD
      • Erasmus Medisch Centrum ( Site 0272)
• Taiwan
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital-GYNECOLOGY ( Site 0033)
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital-Clinical Trial Center ( Site 0032)
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital ( Site 0031)
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06010
    • Gulhane Egitim Arastirma Hastanesi-Onkoloji ( Site 0424)
  • Ankara, Turkey (Türkiye), 06230
    • Hacettepe Universite Hastaneleri-oncology hospital ( Site 0421)
  • Ankara, Turkey (Türkiye), 06680
    • Liv Hospital Ankara-Oncology ( Site 0426)
  • Ankara, Turkey (Türkiye), 06800
    • Ankara Bilkent Şehir Hastanesi ( Site 0427)
  • Istanbul, Turkey (Türkiye), 34722
    • TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 0423)
  • Istanbul
    • Stanbul, Istanbul, Turkey (Türkiye), 34214
      • Medipol Mega Universite Hastanesi-oncology ( Site 0425)
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale-New Haven Hospital-Yale Cancer Center ( Site 0643)
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute ( Site 0642)
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey ( Site 0635)
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute ( Site 0641)
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Main ( Site 0639)
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's University Health Network ( Site 0636)
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center ( Site 0644)
  • Texas
    • Dallas, Texas, United States, 75390-9179
      • UT Southwestern Medical Center-CRO-Simmons Comprehensive Cancer Center ( Site 0645)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: favezelimab/pembrolizumab; IV infusion; Other Names: MK-4280A; Drug: lenvatinib; Oral administration of capsule
Experimental: 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.	Biological: pembrolizumab; IV infusion; Other Names: MK-3475; Keytruda®; Drug: lenvatinib; Oral administration of capsule
Experimental: 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.	Biological: favezelimab/pembrolizumab; IV infusion; Other Names: MK-4280A
Experimental: 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.	Biological: pembrolizumab; IV infusion; Other Names: MK-3475; Keytruda®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Investigator - Cohort B	The ORR is defined as the percentage of participants who have an OR per investigator assessment. The OR is defined as a Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.	Up to approximately 21 months
Clinical Benefit Rate - Cohort A	Clinical benefit rate is defined as the percentage of participants who have clinical benefit. Clinical benefit is defined as major pathologic response (mPR) or pCR in participants who undergo surgery, or clinical complete response (cCR) [defined as residual tumor not visible on clinical exam nor on imaging and a negative biopsy, if biopsy is available, in participants who decline surgery.	Up to approximately 22 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR per RECIST 1.1 as assessed by Investigator - Cohort A	The ORR is defined as the percentage of participants who have an OR per investigator assessment. The OR is defined as a Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.	Up to approximately 22 months
Number of participants with an adverse event (AE) - Cohorts A and B	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of participants who experience an AE will be reported.	Up to approximately 41 months
Number of participants discontinuing from study therapy due to AE - Cohorts A and B	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of participants who discontinue study treatment due to an AE will be reported.	Up to approximately 41 months
Number of participants experiencing perioperative complications - Cohort A	The number of participants who experience perioperative complications will be assessed.	Up to approximately 18 weeks
Pathologic Complete Response (pCR) - Cohort A	pCR is defined as complete absence of viable tumor in the surgical resection sample as assessed by local review of the pathology results. Number of Cohort A participants with pCR will be reported.	Up to approximately 22 months
Major Pathologic Response (mPR) - Cohort A	mPR is defined as the presence of ≤10% of viable tumors in the surgical resection sample as assessed by local review of the pathology results. The number of Cohort A participants with mPR will be reported.	Up to approximately 22 months
Number of participants with an AE that precludes surgery - Cohort A	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of Cohort A participants with an AE that precludes surgery will be reported.	Up to approximately 2 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2023
• Primary Completion (Actual): March 12, 2026
• Study Completion (Actual): March 12, 2026

Study Registration Dates

• First Submitted: August 21, 2023
• First Submitted That Met QC Criteria: September 7, 2023
• First Posted (Actual): September 14, 2023

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Programmed Cell Death-1 (PD1, PD-1); Programmed Cell Death Receptor Ligand 1 (PDL1, PD-L1); Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2); Programmed Cell Death-2 (PD2, PD-2); Lymphocyte-Activation Gene 3 (LAG-3)
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Neoplasms; Endometrial Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; pembrolizumab; lenvatinib
• Other Study ID Numbers: 4280A-010; MK-4280A-010 (Other Identifier: MSD); U1111-1290-7288 (Registry Identifier: UTN); 2023-505022-34-00 (Registry Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No