Background: IDO-1 inhibitors have shown antitumor activity in combination with immunotherapeutic agents in multiple cancers. KHK2455 is a novel and selective oral IDO-1 inhibitor. Unlike other inhibitors, KHK2455 inhibits IDO-1 apo-enzyme, with long-lasting and potent activity. Moga is a monoclonal antibody with enhanced ADCC activity that has shown synergy with KHK2455 in preclinical models. Methods: Pts with advanced solid tumors received escalating doses of KHK2455 alone (0.3, 1, 3, and 10 mg once daily) for 4 weeks (Cycle 0), followed by combination with 1 mg/kg weekly of IV Moga for 4 weeks (Cycle 1) and then on Days 1 and 15 (from Cycle 2) in a standard 3+3 Phase I design. Dose escalation was based on safety, tolerability, pharmacokinetics and IDO activity (kynurenine [Kyn] and tryptophan [Trp] levels and ex vivo Kyn production). Results: 21 pts were enrolled in cohorts that received KHK2455 at 0.3, 1, 3, and 10 mg dose levels. No DLTs were observed. The most frequent adverse events (≥5%) included maculopapular rash, thrush, dysphagia, thrombotic event, and tachycardia, none of which were considered related to KHK2455. One case of rash (Gr 3) was considered related to Moga but not a DLT. Plasma KHK2455 concentrations reached steady state by Day 8 (Cycle 0) and increased dose-dependently. Potent dose-dependent inhibition of IDO activity was demonstrated in plasma samples (67% and 66% inhibition in Kyn concentrations and Kyn:Trp ratio, respectively, compared to baseline) and ex vivo stimulation assays ( > 95% inhibition in Kyn production) at 10 mg KHK2455, confirming target modulation. Four patients (n = 3 head and neck; n = 1 ovarian) from all dosing groups have achieved durable RECIST disease stabilization for more than 6 months, and one (salivary gland carcinoma) for more than 14 months. Conclusions: KHK2455 in combination with Moga is safe and well tolerated at all doses tested, suppresses Kyn production in a dose-dependent and sustained manner, and demonstrates early signals of antitumor activity. These data support the continued development of this promising combination. Clinical trial information: NCT02867007