Study of Favezelimab Coformulated With Pembrolizumab (MK-... | NCT06036836

NCT06036836

ID	Type	Description
MK-4280A-010	Other Identifier	MSD
2023-505022-34-00	Registry Identifier	EU CT
U1111-1290-7288	Registry Identifier	UTN

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.

Name	Type	Description	Arm Group Labels	Other Names
favezelimab/pembrolizumab	Biological	IV infusion	Favezelimab/Pembrolizumab Favezelimab/Pembrolizumab + Lenvatinib (Cohort B)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.](streamdown:incomplete-link)	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

Measure	Description	Time Frame
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

Eligibility Module

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

Label	URL
Merck Clinical Trials Information	View source
Plain Language Summary	View source

ID	Term
D016889	Endometrial Neoplasms
C565324	Parkinson Disease 4, Autosomal Dominant Lewy Body

ID	Term
D014594	Uterine Neoplasms
D005833	Genital Neoplasms, Female
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D014591	Uterine Diseases
D005831	Genital Diseases, Female
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D000091662	Genital Diseases