Study of Pembrolizumab (MK-3475) in Participants With Advanced Melanoma (MK-3475-041/KEYNOTE-041)

Study Overview
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Brief Summary
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This study will assess the safety, tolerability, and efficacy of every-3-week dosing (Q3W) of pembrolizumab (MK-3475) in participants with advanced melanoma; participants may receive pembrolizumab for up to 2 years if deriving clinical benefit. The primary study hypothesis is that treatment with single agent pembrolizumab will result in a clinically meaningful overall response rate.

Detailed Description
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Participants who discontinue pembrolizumab after achieving a complete response (CR) and subsequently develop progressive disease (PD) may be eligible to enter a Second Course Phase and receive pembrolizumab again. The end of the study for each participant will occur with: 1) the marketing approval of pembrolizumab for melanoma, 2) the completion of safety follow up or 3) the time when a possibility of entry to second course of treatment is lost, whichever occurs last.

Official Title
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Phase Ib Study of MK-3475 in Subjects With Advanced Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Biological: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Histologically confirmed diagnosis of locally advanced (unresectable Stage III) or metastatic (Stage IV) melanoma not amenable to local therapy Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 At least one measurable lesion Adequate organ function Exclusion criteria: Prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-PD ligand-1 (PD-L1), anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) agent Is currently participating or has participated in a study with an investigational compound or device within 30 days, or 5X half-life of the investigational compound, whichever is longer, of initial dosing on this study Chemotherapy, targeted small molecule therapy, radiotherapy, or biological cancer therapy (including monoclonal antibodies) within 4 weeks prior to the first dose of trial treatment, or not recovered (<= Grade 1 or baseline) from adverse events due to a previously administered agent Expected to require any other form of systemic or localized antineoplastic therapy while in study Known active central nervous system (CNS) metastases and/or carcinomatous meningitis Documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents Receiving systemic steroid therapy or any other form of immunosuppressive therapy within 1 week prior to the first dose of study treatment Received a live vaccine within 4 weeks prior to the first dose of trial treatment Has a known hypersensitivity to the components of the study drug or another monoclonal antibody History or evidence of active pneumonitis Human immunodeficiency virus (HIV)-positive Has known history of active Hepatitis B or C Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial treatment through 120 days after the last dose of study medication

Ages Eligible for Study
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Minimum Age: 20 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Advanced Cutaneous Melanoma<br>Participants with advanced cutaneous melanoma received pembrolizumab, 2 mg/kg, intravenously (IV) over 30 minutes on Day 1 of each 3-week dosing cycle (Q3W). | Biological: Pembrolizumab<br>* IV infusion<br>* Other names: MK-3475;|
| Experimental: Advanced Mucosal Melanoma<br>Participants with advanced mucosal melanoma received pembrolizumab, 2 mg/kg, IV over 30 minutes on Day 1 Q3W. | Biological: Pembrolizumab<br>* IV infusion<br>* Other names: MK-3475;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Adverse Events (AEs) | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. | All AEs: Up to 30 days after last dose of study drug; Serious AEs: Up to 90 days after last dose of study drug (Up to 27 months) | 
| Number of Participants Discontinuing Treatment Due to AEs | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. | Up to last dose of study drug (Up to 24 months) | 
| Overall Response Rate (ORR) Per Central Radiology Review Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | The ORR, using RECIST 1.1, was defined as the percentage of participants in the analysis population who had a confirmed 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) at any time during the study, based on central radiology review. | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR Per Investigator Assessment Using RECIST 1.1 | The ORR, using RECIST 1.1 criteria, was defined as the percentage of participants in the analysis population who had a confirmed 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) at any time during the study, based on Investigator assessment. | Up to 24 months | 
| ORR Per Central Radiology Review Using Immune-related Response Criteria (irRC) | The ORR, using irRC, was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (irCR; complete disappearance of all tumor lesions, whether measureable or not, and no new lesions) or a Partial Response (irPR; decrease in sum of the products of the 2 largest perpendicular diameters of 50% or greater) at any time during the study, based on central radiology review. | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PD1, PD-1, PDL1, PD-L1