Phase 2 trial of the IDO pathway inhibitor indoximod plus checkpoint inhibition for the treatment of patients with advanced melanoma.

Abstract

9512 Background: The indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to prevent and evade anti-tumor immunity. Inhibitors of the IDO pathway, such as indoximod, are an increasingly validated class of potential cancer therapeutics. Pre-clinical data and an increasing body of clinical data support evaluating the combination of a checkpoint inhibitor (CI) with an IDO pathway inhibitor as potential treatment for advanced melanoma. Methods: Advanced melanoma patients were enrolled in a single arm Phase 2 trial evaluating the addition of indoximod to standard of care CI as approved for melanoma. Prior therapy excluding CI was allowed. Investigators administered their choice of approved CI (pembrolizumab (P), nivolumab (N), ipilimumab (I). Indoximod was administered continuously (1200mg po BID), concurrent CI dosed per approved US label. Study endpoint was best overall response (overall response rate (ORR) = complete response (CR) + partial response (PR)) per site reported RECIST 1.1. Results: 102 patients were enrolled in Phase 2. 70 patients with unresectable stage III or IV cutaneous or mucosal melanoma were treated with P and had an on treatment imaging meeting the per protocol, pre-specified definition of evaluable for efficacy (EE). Additionally, 15 patients had uveal melanoma, 4 received I, 4 received N, and 1 was never treated. 8 patients came off study prior to the first on-treatment imaging study. The ORR for the EE population was 55.7% (39/70, 36 confirmed) with CR of 18.6% (13/70, all confirmed). Median PFS was 12.4 months (95% CI 9.0-NA). Archival tissue was available from 41 of 70 EE patients. The PD-L1 staining ≥ 1% was 54% (22/41). The combination was well tolerated and most common AEs regardless of attribution were fatigue, nausea, pruritus. An additional 21 patients have been enrolled to a biopsy cohort. Conclusions: The combination of indoximod and pembrolizumab demonstrates an ORR of 55.7%, CR 18.6% which compares favorably with reported ORR for P alone (33%). Updated data including biopsy cohort will be presented. Clinical trial information: NCT02073123.