Solid Tumor, Cutaneous Squamous Cell Carcinoma, Endometrial Cancer
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death-2 (PD2, PD-2), Programmed Cell Death Receptor Ligand 1 (PDL1, PD-L1), Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2), Lymphocyte-Activation Gene 3 (LAG-3)
Brief summary
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) \[Cohort B\].
Interventions
BIOLOGICALfavezelimab/pembrolizumab
IV infusion
BIOLOGICALpembrolizumab
IV infusion
DRUGlenvatinib
Oral administration of capsule
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Australia, Canada, France, Germany, Italy, Malaysia, Netherlands, Taiwan, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed