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

Phase 3

Completed

• Conditions: Melanoma
• Interventions: Drug: pembrolizumab + epacadostat; Drug: pembrolizumab + placebo

• Registration Number: NCT02752074
• Lead Sponsor: Incyte Corporation

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-04-22
• Study First Submitted QC: 2016-04-22
• Study First Posted: 2016-04-26
• Study Start: 2016-06-21
• Primary Completion: 2018-01-08
• Results First Submitted: 2019-02-26
• Results First Submitted QC: 2019-05-13
• Results First Posted: 2019-05-15
• Study Completion: 2019-08-16
• Status Verified: 2020-07
• Last Update Submitted: 2020-08-14
• Last Update Posted: 2020-08-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 706

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pembrolizumab + Epacadostat	pembrolizumab + epacadostat	Pembrolizumab + Epacadostat
Pembrolizumab + Placebo	pembrolizumab + placebo	Pembrolizumab + Placebo

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS) Rate at 6 Months	Assessed every 9 weeks of study participation which is estimated to be 24 months. The OS rate at Month 6 was calculated.	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.
Progression-free Survival	Assessed every 9 weeks for duration of study participation which is estimated to be 24 months	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.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Assessed every 9 weeks for duration of study participation which is estimated to be 24 months	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.
Safety and Tolerability, as Assessed by Percentage of Participants With Adverse Events	Through up to 90 days after end of treatment, up to 27 months	Safety and tolerability, as assessed by percentage of participants with adverse events and changes in laboratory parameters.
Duration of Response (DOR)	Assessed every 9 weeks for duration of study participation which is estimated to be 24 months	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.
Apparent Oral Clearance (CL/F) of Epacadostat	Through up to 30 days after the end of treatment, up to 25 months	Defined as oral dose clearance.
Apparent Volume of Distribution (Vd/F) of Epacadostat	Through up to 30 days after the end of treatment, up to 25 months	Apparent volume of distribution after administration.
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	Through up to 30 days after the end of treatment, up to 25 months	Evaluate the measurement of anti-drug antibodies (ADA).