A Study of MK-3475A (Pembrolizumab Formulated With MK-5180) in Japanese Participants With Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma (R/M cSCC) or Locally Advanced (LA) Unresectable cSCC (MK-3475A-E39)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy, safety, and tolerability of subcutaneous (SC) MK-3475A in Japanese participants with recurrent or metastatic cutaneous squamous cell carcinoma or locally advanced unresectable cSCC. The primary hypothesis is that MK-3475A will result in greater than 10% objective response rate (ORR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR).

Official Title
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A Phase 2 Clinical Study to Evaluate the Safety and Efficacy of MK-3475A in Japanese Participants With Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma (R/M cSCC) or Locally Advanced (LA) Unresectable cSCC.

Conditions
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Squamous Cell Carcinoma

Intervention / Treatment
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* Biological: MK-3475A


Participation Criteria
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Eligibility Criteria
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The key inclusion and exclusion criteria include but are not limited to the following: Inclusion Criteria: Has histologically confirmed cSCC by the investigator as the primary site of malignancy R/M cSCC cohort only: Has metastatic disease, defined as disseminated disease distant to the initial/primary site of diagnosis, and/or has locally recurrent disease that has been previously treated (with either surgery or radiotherapy) and is not curable by either surgery or radiotherapy LA unresectable cSCC cohort only: Is ineligible for surgical resection LA unresectable cSCC cohort only: Has received prior radiation therapy (RT) to index site or has been deemed to be not eligible for RT LA unresectable cSCC cohort only: Has received prior systemic therapy for curative intent are eligible regardless of regimen Has a life expectancy of greater than 3 months Must provide archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated Exclusion Criteria: Has cSCC that can be cured with surgical resection, radiotherapy, or with a combination of surgery and radiotherapy. Has any other histologic type of skin cancer other than invasive squamous cell carcinoma as the primary disease under study Has received prior systemic anticancer therapy including investigation agents within 4 weeks before allocation Has not adequately recovered from major surgery or has ongoing surgical complications Received prior radiotherapy within 2 weeks of study intervention, or had radiation-related toxicities, requiring corticosteroids Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention Known additional malignancy that is progressing or has required active treatment within the past 2 years Has an ongoing active infection requiring systemic therapy Has a history of human immunodeficiency virus (HIV) infection Has an active autoimmune disease that has required systemic treatment in past 2 years Has history of allogenic tissue/organ transplant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-3475A<br>Participants will receive MK-3475A subcutaneously for up to 18 administrations. | Biological: MK-3475A<br>* MK-3475A is a fixed-dose formulation of pembrolizumab and MK-5180 for SC administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is defined as the percentage of participants with 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 40 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) | For participants who demonstrate CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented. | Up to approximately 40 months | 
| Disease Control Rate (DCR) | DCR is defined, per RECIST 1.1, as the percentage of participants who demonstrate a confirmed CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of diameters of target lesions), or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD [at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.]).The DCR as assessed by BICR will be presented. | Up to approximately 40 months | 
| Overall Survival (OS) | OS is defined as the time from first dose of study treatment to death due to any cause. | Up to approximately 40 months | 
| Number of Participants who Experience an Adverse Event (AE) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience at least one AE will be reported. | Up to approximately 28 months | 
| Number of Participants who Discontinue Due to an AE | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be reported. | Up to approximately 25 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1(PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)