Background: Arginase, secreted in the tumor microenvironment by myeloid suppressor cells, is a major regulator of arginine-mediated immune response. Arginase inhibition by INCB001158 increases arginine, which reverses the immunosuppressive effects of neutrophils and myeloid-derived suppressor cells on T cells. The current standard first-line (1L) treatment for advanced biliary tract cancers (BTC) is gemcitabine/cisplatin chemotherapy. The combination of INCB001158 immunotherapy and standard 1L treatment may provide additional clinical benefit in pts with advanced or metastatic BTC. Methods: This open-label phase 1/2 study evaluated the safety, tolerability, and antitumor activity of INCB001158 in pts with advanced or metastatic solid tumors. In phase I, dose escalation of INCB001158 (50, 75, and 100 mg twice daily [BID]) was used to determine the recommended phase II dose (RP2D) of INCB001158 + gemcitabine/cisplatin. Phase II used a Simon 2-stage design and evaluated objective response rate (ORR; RECIST v1.1), duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS) of INCB001158 RP2D + gemcitabine (1000 mg/m²)/cisplatin (25 mg/m² Days 1 and 8 of 21-day cycle). Here we report preliminary safety and activity from the cohort of pts with BTC. Results: The phase I dose-escalation group identified a RP2D for INCB001158 of 100 mg BID. At a data cutoff of July 1, 2020, 33 pts with BTC in phase II treated with INCB001158 100 mg BID + gemcitabine/cisplatin were evaluable. Adverse events (AEs) related to INCB001158 and/or chemotherapy occurred in 88% of pts and 73% of pts had AEs related specifically to INCB001158 (Table). Treatment was interrupted due to INCB001158-related TEAEs in 30% of pts (n=10); discontinuation related to INCB001158 occurred in 3% (n=1). Treatment did not result in immune-related or significant additive chemotherapy-associated toxicity. ORR was 24% (8/33; 95% CI, 11.1–42.3) based on confirmed response per investigator’s assessment; stable disease occurred in 42% of pts. Median DOR (95% CI) was 5.8 (4.1–not reached) mo, and the DCR was 67%. Median PFS (95% CI) was 8.5 (5.7–10.1) mo. Conclusions: Preliminary data suggest the combination of INCB001158 100 mg BID + gemcitabine/cisplatin was tolerable and did not result in significant added toxicity. Response rates and PFS suggest that some pts with BTC may benefit from this combination. Clinical trial information: NCT03314935. Preferred Term, n (%)Any GradeGrade ≥3Related to INCB001158Related to Gemcitabine/Cisplatin Fatigue16 (49)3 (9)11 (33)10 (30)Anemia15 (46)7 (21)3 (9)13 (39)Nausea13 (39)2 (6)4 (12)8 (24)Neutrophil count decreased11 (33)10 (30)3 (9)11 (33)Constipation10 (30)01 (3)1 (3)Platelet count decreased10 (30)3 (9)2 (6)10 (30)Vomiting10 (30)4 (12)1 (3)6 (18)Pyrexia9 (27)1 (3)03 (9)