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) \[Cohort B\].
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
160
IV infusion
IV infusion
Oral administration of capsule
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
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.
Time frame: 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.
Time frame: Up to approximately 21 months
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.
Time frame: Up to approximately 22 months
Major Pathologic Response (mPR) - Cohort A
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.
Time frame: Up to approximately 22 months
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.
Time frame: Up to approximately 22 months
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.
Time frame: Up to approximately 41 months
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.
Time frame: Up to approximately 41 months
Number of participants experiencing perioperative complications - Cohort A
The number of participants who experience perioperative complications will be assessed.
Time frame: Up to approximately 18 weeks
Number of participants with an AE that precludes surgery - 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 will be reported.
Time frame: Up to approximately 2 months
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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
...and 34 more locations