A Study of Indoximod or Placebo Plus Pembrolizumab or Nivolumab for Subjects With Unresectable or Metastatic Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Pembrolizumab; Nivolumab; Indoximod
Intervention description: Pembrolizumab will be administered intravenously every 3 weeks starting on day 1.; Nivolumab will be administered intravenously every 2 weeks starting on day 1.; Indoximod will be administered orally every 12 hours starting at Day 1
Intervention MeSH terms: Pembrolizumab; Nivolumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Melanoma, Metastaic Melanoma

Summary:

      This is an adaptive clinical trial that includes a dose escalation phase followed by a
      randomized controlled Phase 3 trial. The purpose of the dose escalation phase is to establish
      the Phase 3 dose of indoximod in combination with pembrolizumab or nivolumab in subjects with
      unresectable or metastatic melanoma and evaluate PK. Subsequently the efficacy, safety and
      tolerability of indoximod plus pembrolizumab or nivolumab versus placebo plus pembrolizumab
      or nivolumab will be studied in subjects with unresectable or metastatic melanoma in the
      Phase 3 portion of the trial.

      The phase 3 study will not proceed per Sponsor decision.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have histologically- or cytologically-confirmed unresectable stage III or stage IV
             melanoma not amenable to local therapy

          -  At least one radiologically measurable lesion as per RECIST 1.1

          -  Have documentation of V600-activating BRAF mutation status or consent to BRAF V600
             mutation testing during the screening period.

          -  ECOG performance status 0 or 1

          -  Ability to ingest oral medications

        Exclusion Criteria:

          -  Has Ocular Melanoma

          -  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 received prior radiotherapy within 2 weeks of therapy.

          -  Is pregnant or breast-feeding 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.

          -  Patients who have active, chronic, or on active treatment for Hep B or Hep C are
             excluded.