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

• ClinicalTrials.gov Identifier: NCT02752074
• Recruitment Status: Completed
• First Posted: April 26, 2016
• Results First Posted: May 15, 2019
• Last Update Posted: August 27, 2020
• Sponsor: Incyte Corporation
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Incyte Corporation

Tracking Information

• First Submitted Date: April 22, 2016
• First Posted Date: April 26, 2016
• Results First Submitted Date: February 26, 2019
• Results First Posted Date: May 15, 2019
• Last Update Posted Date: August 27, 2020
• Actual Study Start Date: June 21, 2016
• Actual Primary Completion Date: January 8, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 14, 2020)

• Progression-free Survival [ Time Frame: 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.
• Overall Survival (OS) Rate at 6 Months [ Time Frame: 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.

Original Primary Outcome Measures (submitted: April 22, 2016)

• Progression-free survival [ Time Frame: Assessed every 9 weeks for duration of study participation which is estimated to be 24 months ]
  Defined as time from date of randomization until the earliest date of disease progression per RECIST 1.1, or death from any cause, whichever comes first.
• Overall survival [ Time Frame: Assessed every 9 weeks for duration of study participation which is estimated to be 24 months ]
  Defined as time from date of randomization to date of death due to any cause.

Current Secondary Outcome Measures (submitted: May 13, 2019)

• Objective Response Rate (ORR) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Through up to 30 days after the end of treatment, up to 25 months ]
  Apparent volume of distribution after administration.
• Clearance (CL) of Pembrolizumab [ Time Frame: Through up to 30 days after the end of treatment, up to 25 months ]
• Volume of Distribution (V) of Pembrolizumab [ Time Frame: Through up to 30 days after the end of treatment, up to 25 months ]
• Formation of Anti-pembrolizumab Antibodies [ Time Frame: Through up to 30 days after the end of treatment, up to 25 months ]
  Evaluate the measurement of anti-drug antibodies (ADA).

Original Secondary Outcome Measures (submitted: April 22, 2016)

• Objective response rate [ Time Frame: Assessed every 9 weeks for duration of study participation which is estimated to be 24 months ]
  Defined as the proportion of subjects who have best response as complete response or partial response based on RECIST 1.1.
• Safety and tolerability, as assessed by adverse events and changes in safety assessments including laboratory parameters [ Time Frame: Through up to 90 days after end of treatment, up to 27 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 3 Study of Pembrolizumab + Epacadostat or Placebo in Subjects With Unresectable or Metastatic Melanoma (Keynote-252 / ECHO-301)
• 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)
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: 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)
• Drug: 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)

Study Arms

• Experimental: Pembrolizumab + Epacadostat
  Pembrolizumab + Epacadostat
  Intervention: Drug: pembrolizumab + epacadostat
• Active Comparator: Pembrolizumab + Placebo
  Pembrolizumab + Placebo
  Intervention: Drug: pembrolizumab + placebo

• Publications *: Long GV, Dummer R, Hamid O, Gajewski TF, Caglevic C, Dalle S, Arance A, Carlino MS, Grob JJ, Kim TM, Demidov L, Robert C, Larkin J, Anderson JR, Maleski J, Jones M, Diede SJ, Mitchell TC. Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study. Lancet Oncol. 2019 Aug;20(8):1083-1097. doi: 10.1016/S1470-2045(19)30274-8. Epub 2019 Jun 17.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 5, 2017): 706
• Original Estimated Enrollment (submitted: April 22, 2016): 600
• Actual Study Completion Date: August 16, 2019
• Actual Primary Completion Date: January 8, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: 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, United States

Administrative Information

• NCT Number: NCT02752074
• Other Study ID Numbers: INCB 24360-301 (ECHO-301)
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Incyte Corporation
• Original Responsible Party: Same as current
• Current Study Sponsor: Incyte Corporation
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC

Investigators

• Study Director: Mark Jones, MD; Incyte Corporation

• PRS Account: Incyte Corporation
• Verification Date: July 2020