Clinical trial NCT06036836: Study of Favezelimab Coformulated With Pembrolizumab (MK-4280A) in Participants With Selected Solid Tumors (MK-4280A-010)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
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)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2023-09-14
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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) \[Cohort B\].


Eligibility criteria: 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

Primary outcomes:
measure: Clinical Benefit Rate - Cohort A
timeFrame: Up to approximately 22 months
measure: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Investigator - Cohort B
timeFrame: Up to approximately 21 months
Secondary outcomes:
measure: Pathologic Complete Response (pCR) - Cohort A
timeFrame: Up to approximately 22 months
measure: Major Pathologic Response (mPR) - Cohort A
timeFrame: Up to approximately 22 months
measure: ORR per RECIST 1.1 as assessed by Investigator - Cohort A
timeFrame: Up to approximately 22 months
measure: Number of participants with an adverse event (AE) - Cohorts A and B
timeFrame: Up to approximately 41 months
measure: Number of participants discontinuing from study therapy due to AE - Cohorts A and B
timeFrame: Up to approximately 41 months
measure: Number of participants experiencing perioperative complications - Cohort A
timeFrame: Up to approximately 18 weeks
measure: Number of participants with an AE that precludes surgery - Cohort A
timeFrame: Up to approximately 2 months
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale-New Haven Hospital-Yale Cancer Center ( Site 0643)
state: Connecticut
city: Boston
country: United States
facility: Dana-Farber Cancer Institute ( Site 0642)
state: Massachusetts
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey ( Site 0635)
state: New Jersey
city: Durham
country: United States
facility: Duke Cancer Institute ( Site 0641)
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Main ( Site 0639)
state: Ohio
city: Bethlehem
country: United States
facility: St. Luke's University Health Network ( Site 0636)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center ( Site 0644)
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center-CRO-Simmons Comprehensive Cancer Center ( Site 0645)
state: Texas
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital-The Kinghorn Cancer Centre ( Site 0005)
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital ( Site 0008)
state: New South Wales
city: Sydney
country: Australia
facility: Blacktown Hospital ( Site 0003)
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital ( Site 0002)
state: Queensland
city: Melbourne
country: Australia
facility: The Alfred Hospital ( Site 0004)
state: Victoria
city: Murdock
country: Australia
facility: Fiona Stanley Hospital ( Site 0006)
state: Western Australia
city: Toronto
country: Canada
facility: Sunnybrook Research Institute ( Site 0607)
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre ( Site 0606)
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital ( Site 0605)
state: Quebec
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal ( Site 0602)
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Centre ( Site 0604)
state: Quebec
city: Quebec City
country: Canada
facility: Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0
state: Quebec
city: Strasbourg
country: France
facility: Institut de cancérologie Strasbourg Europe (ICANS) ( Site 0153)
state: Alsace
city: Brest
country: France
facility: Centre Hospitalier Régional Universitaire de Brest - Hôpital Morvan ( Site 0154)
state: Finistere
city: Lyon Cedex08
country: France
facility: CENTRE LEON BERARD ( Site 0151)
state: Rhone-Alpes
city: Paris
country: France
facility: Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 0155)
city: Essen
country: Germany
facility: Universitaetsklinikum Essen ( Site 0185)
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Universitaetsklinikum Essen-Klinik für Dermatologie, Venerologie und Allergologie ( Site 0182)
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus Dresden-Klinik und Poliklinik für Dermatologie ( Site 0183)
state: Sachsen
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori-SC Oncologia Medica 3 - Tumori Testa-collo ( Site 025
state: Lombardia
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale-s.c. melanoma, immunoterapia oncologica e terapi
city: Johor Bahru
country: Malaysia
facility: Hospital Sultan Ismail-Pusat Rawatan Radioterapi Dan Onkologi ( Site 0063)
state: Johor
city: Lembah Pantai
country: Malaysia
facility: University Malaya Medical Centre ( Site 0061)
state: Kuala Lumpur
city: Kuching
country: Malaysia
facility: Sarawak General Hospital-Radiotherapy Unit ( Site 0062)
state: Sarawak
city: Nijmegen
country: Netherlands
facility: Radboudumc ( Site 0274)
state: Gelderland
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum ( Site 0272)
state: Zuid-Holland
city: Groningen
country: Netherlands
facility: University Medical Center Groningen ( Site 0273)
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital-GYNECOLOGY ( Site 0033)
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital-Clinical Trial Center ( Site 0032)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital ( Site 0031)
city: Stanbul
country: Turkey
facility: Medipol Mega Universite Hastanesi-oncology ( Site 0425)
state: Istanbul
city: Ankara
country: Turkey
facility: Gulhane Egitim Arastirma Hastanesi-Onkoloji ( Site 0424)
city: Ankara
country: Turkey
facility: Hacettepe Universite Hastaneleri-oncology hospital ( Site 0421)
city: Ankara
country: Turkey
facility: Liv Hospital Ankara-Oncology ( Site 0426)
city: Ankara
country: Turkey
facility: Ankara Bilkent Şehir Hastanesi ( Site 0427)
city: Istanbul
country: Turkey
facility: TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 0423)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: