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

Solid Tumor Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06036836
• Other study ID #: 4280A-010
• Secondary ID: MK-4280A-0102023
• Status: Recruiting
• Phase: Phase 2
• Start date: September 29, 2023
• Est. completion date: March 9, 2027

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate pathological 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].

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: March 9, 2027
• Est. primary completion date: March 9, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cutaneous Squamous Cell Carcinoma
• Endometrial Cancer
• Endometrial Neoplasms
• Solid Tumor

Intervention

Biological:
• favezelimab/pembrolizumab
IV infusion
• pembrolizumab
IV infusion

Drug:
• lenvatinib
Oral administration of capsule

Locations

Country	Name	City	State
Australia	Royal Brisbane and Women's Hospital ( Site 0002)	Brisbane	Queensland
Australia	St Vincent's Hospital-The Kinghorn Cancer Centre ( Site 0005)	Darlinghurst	New South Wales
Australia	The Alfred Hospital ( Site 0004)	Melbourne	Victoria
Australia	Fiona Stanley Hospital ( Site 0006)	Murdock	Western Australia
Australia	Royal North Shore Hospital ( Site 0008)	St Leonards	New South Wales
Australia	Blacktown Hospital ( Site 0003)	Sydney	New South Wales
Canada	Jewish General Hospital ( Site 0605)	Montreal	Quebec
Canada	Centre Hospitalier de l'Université de Montréal ( Site 0602)	Montréal	Quebec
Canada	McGill University Health Centre ( Site 0604)	Montréal	Quebec
Canada	Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0	Quebec City	Quebec
Canada	Princess Margaret Cancer Centre ( Site 0606)	Toronto	Ontario
Canada	Sunnybrook Research Institute ( Site 0607)	Toronto	Ontario
France	Centre Hospitalier Régional Universitaire de Brest - Hôpital Morvan ( Site 0154)	Brest	Finistere
France	CENTRE LEON BERARD ( Site 0151)	Lyon Cedex08	Rhone-Alpes
France	Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 0155)	Paris
France	Institut de cancérologie Strasbourg Europe (ICANS) ( Site 0153)	Strasbourg	Alsace
Germany	Universitaetsklinikum Essen-Klinik für Dermatologie, Venerologie und Allergologie ( Site 0182)	Essen	Nordrhein-Westfalen
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori-SC Oncologia Medica 3 - Tumori Testa-collo ( Site 025	Milan	Lombardia
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale-s.c. melanoma, immunoterapia oncologica e terapi	Napoli
Malaysia	Hospital Sultan Ismail-Pusat Rawatan Radioterapi Dan Onkologi ( Site 0063)	Johor Bahru	Johor
Malaysia	Sarawak General Hospital-Radiotherapy Unit ( Site 0062)	Kuching	Sarawak
Malaysia	University Malaya Medical Centre ( Site 0061)	Lembah Pantai	Kuala Lumpur
Netherlands	University Medical Center Groningen ( Site 0273)	Groningen
Netherlands	Radboudumc ( Site 0274)	Nijmegen	Gelderland
Netherlands	Erasmus Medisch Centrum ( Site 0272)	Rotterdam	Zuid-Holland
Taiwan	Taichung Veterans General Hospital-GYNECOLOGY ( Site 0033)	Taichung
Taiwan	National Cheng Kung University Hospital-Clinical Trial Center ( Site 0032)	Tainan
Taiwan	National Taiwan University Hospital ( Site 0031)	Taipei
Turkey	Ankara Bilkent Sehir Hastanesi ( Site 0427)	Ankara
Turkey	Gulhane Egitim Arastirma Hastanesi-Onkoloji ( Site 0424)	Ankara
Turkey	Hacettepe Universite Hastaneleri-oncology hospital ( Site 0421)	Ankara
Turkey	Liv Hospital Ankara-Oncology ( Site 0426)	Ankara
Turkey	TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 0423)	Istanbul
Turkey	Medipol Mega Universite Hastanesi-oncology ( Site 0425)	Stanbul	Istanbul
United States	St. Luke's University Health Network ( Site 0636)	Bethlehem	Pennsylvania
United States	Dana-Farber Cancer Institute ( Site 0642)	Boston	Massachusetts
United States	Cleveland Clinic Main ( Site 0639)	Cleveland	Ohio
United States	UT Southwestern Medical Center-CRO-Simmons Comprehensive Cancer Center ( Site 0645)	Dallas	Texas
United States	Duke Cancer Institute ( Site 0641)	Durham	North Carolina
United States	Rutgers Cancer Institute of New Jersey ( Site 0635)	New Brunswick	New Jersey
United States	Yale-New Haven Hospital-Yale Cancer Center ( Site 0643)	New Haven	Connecticut
United States	UPMC Hillman Cancer Center ( Site 0644)	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Italy,  Malaysia,  Netherlands,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological Complete Response (pCR) - Cohort A	pCR is defined as complete absence of viable tumor in the surgical resection sample as assessed by central review of the pathology results. Number of Cohort A participants with pCR will be reported.	Up to approximately 22 months
Primary	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	Overall Survival (OS) - All Cohorts	OS is defined as the time from randomization to death from any cause.	Up to approximately 41 months
Secondary	Clinical Benefit Rate - Cohort A	Clinical benefit rate is defined as the percentage of participants who have clinical benefit. Clinical benefit is defined as pCR in participants who undergo surgery or clinical complete response (cCR) [defined as residual tumor not visible on clinical exam or on imaging and a negative biopsy, if biopsy is available, in participants who decline surgery.	Up to approximately 22 months
Secondary	Event-Free Survival (EFS) - Cohort A	EFS is defined as the time from randomization to first progression prior to surgical resection as assessed by investigator, inability to resect tumor, recurrence (postsurgical resection), or death from any cause, whichever occurs first.	Up to approximately 41 months
Secondary	Major Pathological Response (mPR) - Cohort A	mPR is defined as =10% of viable tumor cells in the surgical resection sample as assessed by central review of the pathology results. The number of Cohort A participants with mPR will be reported.	Up to approximately 22 months
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of participants experiencing perioperative complications - Cohort A	The number of participants who experience perioperative complications will be assessed.	Up to approximately 18 weeks
Secondary	Number of participants with an AE that precludes surgery/initiation of adjuvant therapy - 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 or initiation of adjuvant therapy will be reported.	Up to approximately 2 months
Secondary	Progression Free Survival (PFS) - Cohort B	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by the investigator. Per RECIST 1.1, or by histopathologic confirmation of disease progression (PD), PD is defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions is also considered PD. Unequivocal progression of non-target lesions is also considered PD.	Up to approximately 41 months
Secondary	Duration of Response (DOR) - Cohort B	DOR is defined as the time from first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by Blinded Independent Central Review (BICR) will be presented.	Up to approximately 41 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary