Abstract 5481: Combination therapy with anti-PD-1 and YH29407, a novel IDO1 inhibitor, enhances T cell-mediated antitumor immunity in MC38 tumor-bearing mice

Background: The IDO is an enzyme responsible for catabolizing tryptophan (Trp) to kynurenine (Kyn). The kynurenine exert important immunosuppressive functions by activating Treg cells and myeloid-derived suppressor cells. YH29407 is a novel IDO1 inhibitor, improved the pharmacodynamics compared to previous IDO inhibitors. Methods: To evaluate antitumor effects and immune profiles of YH29407, YH29407 was dosed at 50 or 100 mg/kg twice daily (B.I.D.) alone or in combination with anti-PD-1 (10 mg/kg, B.I.W., i.p.) and BMS-986205 was dosed at 125 mg/kg once daily (Q.D.) alone or in combination with anti-PD-1 in a MC38 syngeneic tumor model. The antitumor effects during 11 days of administration of YH29407 alone or combinations and BMS-986205 alone or combination in the MC38 model were measured. Measurements were carried out up to day 50 for survival testing. After 3 days of treatment for each condition, immune cell profiles were evaluated by flow cytometry. Results: The YH29407 at dose of 100 mg/kg B.I.D combination treatment group showed the best effects on tumor size reduction. The group constituting >TGI:70% contained 100% (15/15) of the combination treatment group, whereas 15% (2/13) of competitor BMS-986205 combination group were contained. In addition, in the combination treatment group, most tumors showed an aspect of decrease including complete responses of 5 mice. Moreover, there was a complete response in YH29407 alone group but, not observed in BMS-986205 group. According to flow cytometry analysis, the combination treatment group showed higher CD3+ total T cells compared to the vehicle group (*p