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

Melanoma Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02752074
• Other study ID #: INCB 24360-301 (ECHO-301)
• Status: Completed
• Phase: Phase 3
• Start date: June 21, 2016
• Est. completion date: August 16, 2019

Study information

• Verified date: July 2020
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 706
• Est. completion date: August 16, 2019
• Est. primary completion date: January 8, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Melanoma

Intervention

Drug:
• pembrolizumab + epacadostat
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)
• pembrolizumab + placebo
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)

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Incyte Corporation	Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Chile,  Denmark,  France,  Germany,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  New Zealand,  Poland,  Russian Federation,  South Africa,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Clearance (CL) of Pembrolizumab		Through up to 30 days after the end of treatment, up to 25 months
Secondary	Volume of Distribution (V) of Pembrolizumab		Through up to 30 days after the end of treatment, up to 25 months
Secondary	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