A Phase 3 Study of Pembrolizumab + Epacadostat or Placebo in Subjects With Unresectable or Metastatic Melanoma (Keynote-252 / ECHO-301)

Study Overview
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Brief Summary
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The purpose of the study is to assess the efficacy, safety, and tolerability when combining pembrolizumab with epacadostat or placebo in participants with unresectable or metastatic melanoma

Official Title
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A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study of Pembrolizumab (MK-3475) in Combination With Epacadostat or Placebo in Subjects With Unresectable or Metastatic Melanoma (Keynote-252 / ECHO-301)

Conditions
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Melanoma

Intervention / Treatment
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* Drug: pembrolizumab + epacadostat
* Drug: pembrolizumab + placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have histologically or cytologically confirmed melanoma Have unresectable Stage III or Stage IV melanoma, as per AJCC staging system not amenable to local therapy A minimum of 1 measurable lesion by CT or MRI Provide a baseline tumor biopsy Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 Exclusion Criteria: Has received prior systemic treatment for unresectable or metastatic melanoma (except BRAF directed therapy) Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or IDO1 inhibitor or any other antibody or drug specifically targeting checkpoint pathways other than anti-CTLA-4 which is permitted in the adjuvant setting Has received prior adjuvant therapy, monoclonal antibody or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer) Has an active infection requiring systemic therapy Has known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) Has known history of or is positive for Hepatitis B or Hepatitis C Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pembrolizumab + Epacadostat<br>Pembrolizumab + Epacadostat | Drug: pembrolizumab + epacadostat<br>* Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1) Epacadostat will be administered orally daily starting at Day 1 (Week 1)<br>|
| Active Comparator: Pembrolizumab + Placebo<br>Pembrolizumab + Placebo | Drug: pembrolizumab + placebo<br>* Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1) Placebo will be administered orally daily starting at Day 1 (Week 1)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression-free survival, defined as the time from date of randomization until the earliest date of disease progression, as determined by independent central review of objective radiographic disease assessments per RECIST 1.1, or death from any cause, whichever comes first. | Assessed every 9 weeks for duration of study participation which is estimated to be 24 months | 
| Overall Survival (OS) Rate at 6 Months | Defined as time from date of randomization to date of death due to any cause. OS was calculated using product-limit (Kaplan-Meier) method for censored data. | Assessed every 9 weeks of study participation which is estimated to be 24 months. The OS rate at Month 6 was calculated. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective response rate (ORR) is defined as the percentage of the participants in the analysis population who have a confirmed complete response (CR) or partial response (PR) based on RECIST 1.1 by independent central review. | Assessed every 9 weeks for duration of study participation which is estimated to be 24 months | 
| Safety and Tolerability, as Assessed by Percentage of Participants With Adverse Events | Safety and tolerability, as assessed by percentage of participants with adverse events and changes in laboratory parameters. | Through up to 90 days after end of treatment, up to 27 months | 
| Duration of Response (DOR) | Defined as the time from the earliest date of qualifying response until earliest date of disease progression, per RECIST v1.1, or death from any cause, whichever comes first. Includes participants with complete response or partial response. | Assessed every 9 weeks for duration of study participation which is estimated to be 24 months | 
| Apparent Oral Clearance (CL/F) of Epacadostat | Defined as oral dose clearance. | Through up to 30 days after the end of treatment, up to 25 months | 
| Apparent Volume of Distribution (Vd/F) of Epacadostat | Apparent volume of distribution after administration. | Through up to 30 days after the end of treatment, up to 25 months | 
| Clearance (CL) of Pembrolizumab |  | Through up to 30 days after the end of treatment, up to 25 months | 
| Volume of Distribution (V) of Pembrolizumab |  | Through up to 30 days after the end of treatment, up to 25 months | 
| Formation of Anti-pembrolizumab Antibodies | Evaluate the measurement of anti-drug antibodies (ADA). | Through up to 30 days after the end of treatment, up to 25 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma, Metastatic Melanoma