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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02752074
Recruitment Status : Completed
First Posted : April 26, 2016
Results First Posted : May 15, 2019
Last Update Posted : September 4, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Incyte Corporation

Tracking Information
First Submitted Date  ICMJE April 22, 2016
First Posted Date  ICMJE April 26, 2016
Results First Submitted Date  ICMJE February 26, 2019
Results First Posted Date  ICMJE May 15, 2019
Last Update Posted Date September 4, 2019
Actual Study Start Date  ICMJE May 31, 2016
Actual Primary Completion Date January 8, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 13, 2019)
  • Progression-free Survival [ Time Frame: Assessed every 9 weeks for duration of study participation which is estimated to be 24 months or data cut-off 08Jan2018 ]
    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  ICMJE
 (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.
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE A Phase 3 Study of Pembrolizumab + Epacadostat or Placebo in Subjects With Unresectable or Metastatic Melanoma (Keynote-252 / ECHO-301)
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Melanoma
Intervention  ICMJE
  • 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  ICMJE
  • 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 5, 2017)
706
Original Estimated Enrollment  ICMJE
 (submitted: April 22, 2016)
600
Actual Study Completion Date  ICMJE August 16, 2019
Actual Primary Completion Date January 8, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE 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
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02752074
Other Study ID Numbers  ICMJE INCB 24360-301 (ECHO-301)
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Incyte Corporation
Study Sponsor  ICMJE Incyte Corporation
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Study Director: Mark Jones, MD Incyte Corporation
PRS Account Incyte Corporation
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP