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

NCT06036836 | Completed Phase 2 DMC FDA Drug

• 4 other identifiers: 4280A-010MK-4280A-0102023-505022-34-00U1111-1290-7288
• Study Type: interventional
• Target: 163
• Locations: 10 countries
• Sites: 44

Brief Summary

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) \[Cohort B\].

Conditions

Solid Tumor; Cutaneous Squamous Cell Carcinoma; Endometrial Cancer

Keywords

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)

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (7)

• Pathologic Complete Response (pCR) - Cohort A

  Up to approximately 22 months

• Major Pathologic Response (mPR) - Cohort A

  Up to approximately 22 months

• ORR per RECIST 1.1 as assessed by Investigator - Cohort A

  Up to approximately 22 months

• Number of participants with an adverse event (AE) - Cohorts A and B

  Up to approximately 41 months

• Number of participants discontinuing from study therapy due to AE - Cohorts A and B

  Up to approximately 41 months

Study Arms (4)

Favezelimab/Pembrolizumab

EXPERIMENTAL

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

Pembrolizumab

EXPERIMENTAL

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

Favezelimab/Pembrolizumab + Lenvatinib (Cohort B)

EXPERIMENTAL

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; Drug: lenvatinib

Pembrolizumab + Lenvatinib (Cohort B)

EXPERIMENTAL

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; Drug: lenvatinib

Interventions

favezelimab/pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-4280A

Favezelimab/Pembrolizumab; Favezelimab/Pembrolizumab + Lenvatinib (Cohort B)

pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475, Keytruda®

Pembrolizumab; Pembrolizumab + Lenvatinib (Cohort B)

lenvatinib DRUG

Oral administration of capsule

Favezelimab/Pembrolizumab + Lenvatinib (Cohort B); Pembrolizumab + Lenvatinib (Cohort B)

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Cohort A Only - Participant is an individual of any sex/gender Cohort B Only - Participant is assigned female sex at birth
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (44)

Yale-New Haven Hospital-Yale Cancer Center ( Site 0643)

New Haven, Connecticut, 06510, United States

Location

Dana-Farber Cancer Institute ( Site 0642)

Boston, Massachusetts, 02215, United States

Location

Rutgers Cancer Institute of New Jersey ( Site 0635)

New Brunswick, New Jersey, 08903, United States

Location

Duke Cancer Institute ( Site 0641)

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic Main ( Site 0639)

Cleveland, Ohio, 44195, United States

Location

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

Bethlehem, Pennsylvania, 18015, United States

Location

UPMC Hillman Cancer Center ( Site 0644)

Pittsburgh, Pennsylvania, 15232, United States

Location

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

Dallas, Texas, 75390-9179, United States

Location

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

Darlinghurst, New South Wales, 2010, Australia

Location

Royal North Shore Hospital ( Site 0008)

St Leonards, New South Wales, 2065, Australia

Location

Blacktown Hospital ( Site 0003)

Sydney, New South Wales, 2148, Australia

Location

Royal Brisbane and Women's Hospital ( Site 0002)

Brisbane, Queensland, 4029, Australia

Location

The Alfred Hospital ( Site 0004)

Melbourne, Victoria, 3004, Australia

Location

Fiona Stanley Hospital ( Site 0006)

Murdock, Western Australia, 6150, Australia

Location

Sunnybrook Research Institute ( Site 0607)

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Cancer Centre ( Site 0606)

Toronto, Ontario, M5G 2M9, Canada

Location

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

Montreal, Quebec, H2X 3E4, Canada

Location

Jewish General Hospital ( Site 0605)

Montreal, Quebec, H3T 1E2, Canada

Location

McGill University Health Centre ( Site 0604)

Montreal, Quebec, H4A 3J1, Canada

Location

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

Québec, Quebec, G1J 1Z4, Canada

Location

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

Strasbourg, Alsace, 67200, France

Location

CENTRE LEON BERARD ( Site 0151)

Lyon Cedex08, Auvergne-Rhône-Alpes, 69373, France

Location

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

Brest, Finistere, 29200, France

Location

Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 0155)

Paris, 75014, France

Location

Universitaetsklinikum Essen ( Site 0185)

Essen, North Rhine-Westphalia, 45147, Germany

Location

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

Essen, North Rhine-Westphalia, 45147, Germany

Location

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

Dresden, Saxony, 01307, Germany

Location

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

Milan, Lombardy, 20133, Italy

Location

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

Naples, 80131, Italy

Location

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

Johor Bahru, Johor, 81100, Malaysia

Location

University Malaya Medical Centre ( Site 0061)

Lembah Pantai, Kuala Lumpur, 59100, Malaysia

Location

Sarawak General Hospital-Radiotherapy Unit ( Site 0062)

Kuching, Sarawak, 93586, Malaysia

Location

Radboudumc ( Site 0274)

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Erasmus Medisch Centrum ( Site 0272)

Rotterdam, South Holland, 3015 GD, Netherlands

Location

University Medical Center Groningen ( Site 0273)

Groningen, 9713GZ, Netherlands

Location

Taichung Veterans General Hospital-GYNECOLOGY ( Site 0033)

Taichung, 407, Taiwan

Location

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

Tainan, 704, Taiwan

Location

National Taiwan University Hospital ( Site 0031)

Taipei, 10002, Taiwan

Location

Medipol Mega Universite Hastanesi-oncology ( Site 0425)

Stanbul, Istanbul, 34214, Turkey (Türkiye)

Location

Gulhane Egitim Arastirma Hastanesi-Onkoloji ( Site 0424)

Ankara, 06010, Turkey (Türkiye)

Location

Hacettepe Universite Hastaneleri-oncology hospital ( Site 0421)

Ankara, 06230, Turkey (Türkiye)

Location

Liv Hospital Ankara-Oncology ( Site 0426)

Ankara, 06680, Turkey (Türkiye)

Location

Ankara Bilkent Şehir Hastanesi ( Site 0427)

Ankara, 06800, Turkey (Türkiye)

Location

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

Istanbul, 34722, Turkey (Türkiye)

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Endometrial Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2023
• First Posted: September 14, 2023
• Study Start: September 29, 2023
• Primary Completion: March 12, 2026
• Study Completion: March 12, 2026
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

NL (3); AU (6); DE (3); CA (6); US (8); TU (6); FR (4); IT (2); MY (3); TW (3)