Phase I study of the indoleamine 2,3-dioxygenase 1 inhibitor navoximod (GDC-0919) as monotherapy and in combination with the PD-L1 inhibitor atezolizumab in Japanese patients with advanced solid tumours

Summary Navoximod (GDC-0919) is a small molecule inhibitor of indoleamine-2,3-dioxygenase 1. This study investigated the safety, tolerability and pharmacokinetics of navoximod alone and in combination with atezolizumab in Japanese patients with advanced solid tumours. This was a phase I, open-label, dose-escalation study. Patients received monotherapy with navoximod 400 mg, 600 mg or 1000 mg orally twice daily (BID) in Stage 1 and navoximod 200 mg, 400 mg, 600 mg or 1000 mg orally BID plus atezolizumab 1200 mg intravenously every 21 days in Stage 2. Objectives included safety, tolerability, efficacy and pharmacokinetic outcomes.Overall, 20 patients were enrolled (Stage 1: n = 10; Stage 2: n = 10). No dose-limiting toxicities were observed. In Stage 1, treatment-related adverse events (TRAEs) of any grade that occurred in ≥20% of patients were chromaturia (50%) and maculopapular rash (20%). Grade ≥ 3 TRAEs were reported in two patients (20%; maculopapular rash and lipase increased). In Stage 2, TRAEs that occurred in ≥30% of patients were chromaturia (60%) and, decreased appetite (40%). Grade ≥ 3 TRAEs were reported in three patients (30%; hyponatraemia, aspartate aminotransferase increased, alanine aminotransferase increased, lymphopaenia and neutropaenia). Stable disease was observed in five patients (50%) in Stage 1 and eight patients (80%) in Stage 2. Navoximod showed linear pharmacokinetics. The recommended dose of navoximod monotherapy was determined as 1000 mg orally BID, and could be considered 1000 mg orally BID in combination with atezolizumab. Navoximod as monotherapy and in combination with atezolizumab was well tolerated in Japanese patients with advanced solid tumours.