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).

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 14

Inclusion Criteria

- Have histologically or cytologically confirmed melanoma.
- Have unresectable Stage III or Stage IV melanoma, not amenable to local therapy.
- Have been untreated for advanced or metastatic disease - with exceptions as outlined in the protocol.
- Have documentation of V600-activating BRAF mutation status or consent to BRAF V600 mutation testing during the screening period.
- Have laboratory parameters within Protocol-defined range.
- Have the presence of at least one measurable lesion by CT or MRI per RECIST 1.1 criteria.
- Provide a baseline tumor biopsy
- Have resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia).
- Have an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
subject.

Exclusion Criteria

- Has received prior systemic treatment for unresectable or metastatic melanoma (except therapy as noted in inclusion criteria #3).
- 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, chemotherapy or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer) before administration of study drug or not recovered (* Grade 1 or at baseline) from AEs due to previously administered agents. Exception to this rule would be use of denosumab, which is not excluded.
Note: Subjects with * Grade 2 neuropathy are an exception and may enroll.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions are described in the protocol.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Has ocular melanoma.
- Has an active autoimmune disease that has required systemic treatment in past 2 years.
- Has an active infection requiring systemic therapy.
- Has known history of human immunodeficiency virus (HIV)
- Has known history of or is positive for Hepatitis B or Hepatitis C
- Has history of (noninfectious) pneumonitis that required steroids, or current pneumonitis.
- Has received prior radiotherapy within 2 weeks of therapy. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study.
- Has received live vaccine within 30 days before the first dose of study treatment.
- Has received monoamine oxidase inhibitors within the 21 days prior to starting study treatment.
- Has any history of Serotonin Syndrome after receiving serotonergic drugs.
- Has presence of a gastrointestinal condition that may affect drug absorption.
- Has a history or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful.
- Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, and arrhythmia requiring therapy. Medically controlled arrhythmia would be permitted.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The dual primary endpoints are PFS and OS.<br /><br>* Progression-free survival, defined as the time from date of randomization<br /><br>until the<br /><br>earliest date of disease progression, as determined by independent central<br /><br>review of<br /><br>objective radiographic disease assessments per RECIST 1.1, or death from any<br /><br>cause,<br /><br>whichever comes first.<br /><br>* Overall survival, defined as the time from date of randomization to date of<br /><br>death due to<br /><br>any cause.<br /><br>The study is considered to have met its study objective if the combination is<br /><br>superior to<br /><br>pembrolizumab and placebo in either PFS or OS.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Objective response rate, defined as the proportion of subjects who have best<br /><br>response as<br /><br>complete response (CR) or partial response (PR). Responses are based on<br /><br>independent<br /><br>central review using RECIST 1.1.<br /><br>Duration of response (DOR) determined by disease assessment defined as the time<br /><br>from<br /><br>the earliest date of qualifying response until earliest date of disease<br /><br>progression or death<br /><br>from any cause, whichever comes first. Response will be determined by<br /><br>independent<br /><br>central review using RECIST 1.1.</p><br>