A Study of Indoximod or Placebo Plus Pembrolizumab or Nivolumab for Subjects With Unresectable or Metastatic Melanoma

A Phase 2/3 (Adaptive Design) Study of the Concomitant Administration of Indoximod or Placebo Plus Pembrolizumab or Nivolumab in Adult Patients With Unresectable Stage III or Stage IV Malignant Melanoma

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.

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.