Preliminary results from a phase 1/2 study of INCB024360 combined with ipilimumab (ipi) in patients (pts) with melanoma.

3010 Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is a tryptophan-catabolizing enzyme that is overexpressed in cancers and induces immune tolerance by suppressing T-cell responses. INCB024360, a potent, selective IDO1 inhibitor, was generally well tolerated as monotherapy up to 700 mg BID. Preclinical data support anti-tumor synergy for INCB024360 when administered with antibody antagonists to checkpoint receptors. Methods: This is an ongoing dose-escalation study of INCB024360 combined with ipi (3 mg/kg IV q 3 wks x 4) in pts with metastatic melanoma. Enrollment in 2 cohorts (300 mg BID, 25 mg BID) is complete. Toxicity, ORR (irRC), Duration of Response (DoR), and OS were evaluated. The DLT evaluation period was 8 wks andassessments for response were every 9 wks. Results: Seven pts were enrolled at 300 mg BID. When 5 pts developed clinically significant ALT elevations after 30–76 days on treatment, enrollment was stopped. ALT elevations were reversible with corticosteroids and treatment discontinuati...