Study of Favezelimab Coformulated With Pembrolizumab (MK-4280A) in Participants With Selected Solid Tumors (MK-4280A-010)
- Conditions
- Cutaneous Squamous Cell CarcinomaEndometrial CancerSolid Tumor
- Interventions
- Registration Number
- NCT06036836
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief 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) \[Cohort B\].
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 160
Not provided
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pembrolizumab + Lenvatinib (Cohort B) lenvatinib 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. Favezelimab/Pembrolizumab + Lenvatinib (Cohort B) lenvatinib 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. Favezelimab/Pembrolizumab + Lenvatinib (Cohort B) favezelimab/pembrolizumab 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. Favezelimab/Pembrolizumab favezelimab/pembrolizumab 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. Pembrolizumab pembrolizumab 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. Pembrolizumab + Lenvatinib (Cohort B) pembrolizumab 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.
- Primary Outcome Measures
Name Time Method Clinical Benefit Rate - Cohort A Up to approximately 22 months 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.
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Investigator - Cohort B Up to approximately 21 months 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.
- Secondary Outcome Measures
Name Time Method Pathologic Complete Response (pCR) - Cohort A Up to approximately 22 months 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.
Major Pathologic Response (mPR) - Cohort A Up to approximately 22 months mPR is defined as the presence of ≤10% of viable tumors in the surgical resection sample as assessed by local review of the pathology results. The number of Cohort A participants with mPR will be reported.
ORR per RECIST 1.1 as assessed by Investigator - Cohort A Up to approximately 22 months 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.
Number of participants with an adverse event (AE) - Cohorts A and B Up to approximately 41 months 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.
Number of participants discontinuing from study therapy due to AE - Cohorts A and B Up to approximately 41 months 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.
Number of participants experiencing perioperative complications - Cohort A Up to approximately 18 weeks The number of participants who experience perioperative complications will be assessed.
Number of participants with an AE that precludes surgery - Cohort A Up to approximately 2 months 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 will be reported.
Trial Locations
- Locations (44)
Yale-New Haven Hospital-Yale Cancer Center ( Site 0643)
🇺🇸New Haven, Connecticut, United States
Dana-Farber Cancer Institute ( Site 0642)
🇺🇸Boston, Massachusetts, United States
Rutgers Cancer Institute of New Jersey ( Site 0635)
🇺🇸New Brunswick, New Jersey, United States
Duke Cancer Institute ( Site 0641)
🇺🇸Durham, North Carolina, United States
Cleveland Clinic Main ( Site 0639)
🇺🇸Cleveland, Ohio, United States
St. Luke's University Health Network ( Site 0636)
🇺🇸Bethlehem, Pennsylvania, United States
UPMC Hillman Cancer Center ( Site 0644)
🇺🇸Pittsburgh, Pennsylvania, United States
UT Southwestern Medical Center-CRO-Simmons Comprehensive Cancer Center ( Site 0645)
🇺🇸Dallas, Texas, United States
St Vincent's Hospital-The Kinghorn Cancer Centre ( Site 0005)
🇦🇺Darlinghurst, New South Wales, Australia
Royal North Shore Hospital ( Site 0008)
🇦🇺St Leonards, New South Wales, Australia
Scroll for more (34 remaining)Yale-New Haven Hospital-Yale Cancer Center ( Site 0643)🇺🇸New Haven, Connecticut, United States