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

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 2

Conditions: Endometrial Cancer; Solid Tumor; Cutaneous Squamous Cell Carcinoma

Treatments: Drug: lenvatinib; Biological: pembrolizumab; Biological: favezelimab/pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06036836

2023-505022-34 (Registry Identifier)

U1111-1290-7288 (Other Identifier)

MK-4280A-010 (Other Identifier)

4280A-010

Details and patient eligibility

About

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].

Enrollment: 160 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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160 participants in 4 patient groups

Favezelimab/Pembrolizumab

Experimental group

Description:

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.

Treatment:

Biological: favezelimab/pembrolizumab

Pembrolizumab

Experimental group

Description:

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.

Treatment:

Biological: pembrolizumab

Favezelimab/Pembrolizumab + Lenvatinib (Cohort B)

Experimental group

Description:

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.

Treatment:

Biological: favezelimab/pembrolizumab

Drug: lenvatinib

Pembrolizumab + Lenvatinib (Cohort B)

Experimental group

Description:

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.

Treatment:

Biological: pembrolizumab

Drug: lenvatinib