MelanomaPhase 3NCT02752074
A Phase 3 Study of Pembrolizumab + Epacadostat or Placebo in Subjects With Unresectable or Metastatic Melanoma (Keynote-252 / ECHO-301)
A Phase 3 study testing pembrolizumab + epacadostat in people with Melanoma, run by Incyte Corporation at 129 sites in 23 countries.
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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- pembrolizumab + epacadostat
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 706 participants
- Where
- 129 sitesin 23 countries
- Study dates
- 21 Jun 2016to 16 Aug 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
129 sites in 23 countries.
129 sites in 23 countries
United States34 sites
Study site
Ann Arbor, Michigan
Study site
Aurora, Colorado
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Austin, Texas
Study site
Billings, Montana
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Birmingham, Alabama
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Boston, Massachusetts
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Charlotte, North Carolina
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Chicago, Illinois
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Dallas, Texas
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Denver, Colorado
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Fairfax, Virginia
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Fort Lauderdale, Florida
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Fridley, Minnesota
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Iowa City, Iowa
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Jacksonville, Florida
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Kansas City, Kansas
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Las Vegas, Nevada
Study site
Little Rock, Arkansas
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Los Angeles, California
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Lutherville, Maryland
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Nashville, Tennessee
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Ocala, Florida
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Omaha, Nebraska
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Peoria, Illinois
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Philadelphia, Pennsylvania
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Rochester, New York
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Salt Lake City, Utah
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San Francisco, California
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Santa Barbara, California
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Santa Monica, California
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Scottsdale, Arizona
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Spokane, Washington
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Washington D.C., District of Columbia
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West Palm Beach, Florida
Japan17 sites
Study site
Asahikawa
Study site
Chūō
Study site
Fukuoka
Study site
Kagoshima
Study site
Kumamoto
Study site
Kurume
Study site
Kyoto
Study site
Matsumoto
Study site
Nagoya
Study site
Niigata
Study site
Okayama
Study site
Osaka
Study site
Sapporo
Study site
Sendai
Study site
Susono, Sunto-gun
Study site
Tokyo
Study site
Tsukuba
France9 sites
Study site
Bordeaux
Study site
Lille
Study site
Marseille
Study site
Paris
Study site
Pierre-Bénite
Study site
Reims
Study site
Rennes
Study site
Toulouse
Study site
Villejuif
Spain8 sites
Study site
A Coruña
Study site
Barcelona
Study site
Donostia / San Sebastian, Guipuzcoa
Study site
Donostia / San Sebastian
Study site
Madrid
Study site
Pamplona
Study site
Seville
Study site
Valencia
Australia7 sites
Study site
Cairns, Queensland
Study site
Camperdown, New South Wales
Study site
Greenslopes, Queensland
Study site
Kurralta Park, South Australia
Study site
Melbourne, Victoria
Study site
Westmead, New South Wales
Study site
Wollstonecraft, New South Wales
Italy6 sites
Study site
Bergamo
Study site
Genova
Study site
Milan
Study site
Naples
Study site
Padova
Study site
Siena
Germany5 sites
Study site
Buxtehude
Study site
Essen
Study site
Hanover
Study site
Kiel
Study site
Tübingen
South Africa5 sites
Study site
Cape Town, Western Cape
Study site
Groenkloof, Pretoria
Study site
Johannesburg, Gauteng
Study site
Kraaifontein
Study site
Sandton, Gauteng
Canada4 sites
Study site
Montreal, Quebec
Study site
North Vancouver, British Columbia
Study site
Ottawa, Ontario
Study site
Toronto, Ontario
Mexico4 sites
Study site
Chihuahua City
Study site
Distrito Federal
Study site
Mexico City
Study site
Monterrey
Sweden4 sites
Study site
Gothenburg
Study site
Lund
Study site
Stockholm
Study site
Uppsala
Switzerland3 sites
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Geneva
Study site
Lausanne
Study site
Zurich, Canton of Zurich
United Kingdom3 sites
Study site
Edinburgh
Study site
London
Study site
Manchester
About this study
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)
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
- Conditions
- Melanoma
- Being tested
- pembrolizumab + epacadostat, pembrolizumab + placebo
- Keywords
- Melanoma, Metastatic Melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pembrolizumab + epacadostatDrug
- 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 + placeboDrug
- 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 group | Role | What they receive |
|---|---|---|
| Pembrolizumab + Epacadostat | Experimental | Pembrolizumab + Epacadostat Receives: Drug: pembrolizumab + epacadostat |
| Pembrolizumab + Placebo | Active comparator | Pembrolizumab + Placebo Receives: Drug: pembrolizumab + placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Assessed every 9 weeks of study participation which is estimated to be 24 months. The OS rate at Month 6 was calculated.
Secondary outcomes (8)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Through up to 30 days after the end of treatment, up to 25 months
Clearance (CL) of Pembrolizumab
Measured: Through up to 30 days after the end of treatment, up to 25 months
Volume of Distribution (V) of Pembrolizumab
Measured: 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).
Measured: Through up to 30 days after the end of treatment, up to 25 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2016 (estimated)
- Study start21 Jun 2016
- Primary completion8 Jan 2018
- Study completion16 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Incyte CorporationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 706 participants (actual)
Sponsor and investigators
- Lead sponsor
- Incyte Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Mark Jones, MD, Study director, Incyte Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02752074
- Sponsor's protocol ID
- INCB 24360-301 (ECHO-301)
- Other IDs
- 2015-004991-31, 2015
- Status last verified
- Aug 2025
- First submitted
- 22 Apr 2016
- Last updated
- 24 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
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.
PubMed 31221619
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02752074
- Acronym / sponsor ID
- INCB 24360-301 (ECHO-301)
- Conditions
- Melanoma
- Keywords
- Melanoma, Metastatic Melanoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 706 participants (actual)
- Lead sponsor
- Incyte CorporationIndustry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 21 Jun 2016 (actual)
- Primary completion
- 8 Jan 2018 (actual)
- Study completion
- 16 Aug 2019 (actual)
- First posted
- 26 Apr 2016 (estimated)
- Results
- Posted 15 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab + Epacadostat | Experimental | Drug: pembrolizumab + epacadostatPembrolizumab + Epacadostat |
| Pembrolizumab + Placebo | Active comparator | Drug: pembrolizumab + placeboPembrolizumab + Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 + Epacadostat |
| 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) | Drug | Pembrolizumab + Placebo |
Primary outcome
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.
8 secondary outcomes
Objective Response Rate (ORR)
Time frame: 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
Time frame: Through up to 90 days after end of treatment, up to 27 months
Duration of Response (DOR)
Time frame: Assessed every 9 weeks for duration of study participation which is estimated to be 24 months
Apparent Oral Clearance (CL/F) of Epacadostat
Time frame: Through up to 30 days after the end of treatment, up to 25 months
Apparent Volume of Distribution (Vd/F) of Epacadostat
Time frame: Through up to 30 days after the end of treatment, up to 25 months
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31221619Long 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Jones, MD study director
Incyte Corporation
129 sites in 23 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing pembrolizumab + epacadostat in people with Melanoma, run by Incyte Corporation at 129 sites in 23 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 129 sites in United States, Japan, France, Spain, Australia and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (time frame: Assessed every 9 weeks for duration of study participation which is estimated to be 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02752074, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2025.