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Ref Type Journal Article
PMID (31124055)
Authors Ebata T, Shimizu T, Fujiwara Y, Tamura K, Kondo S, Iwasa S, Yonemori K, Shimomura A, Kitano S, Koyama T, Sato N, Nakai K, Inatani M, Yamamoto N
Title 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.
Journal Investigational new drugs
Vol 38
Issue 2
Date 2020 04
URL
Abstract Text 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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
GDC-0919 Navoximod|NLG919|RG6078 IDO1 Inhibitor 10 Immune Checkpoint Inhibitor 94 GDC-0919 (Navoximod) inhibits indoleamine 2,3-dioxygenase 1 (IDO1) to prevent tryptophan breakdown in the tumor microenvironment, thereby activating a cytotoxic immune response against IDO1 expressing tumor cells (PMID: 25054064, PMID: 31124055).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown Advanced Solid Tumor not applicable Atezolizumab + GDC-0919 Phase I Actionable In a Phase I trial, GDC-0919 (Navoximod) and Tecentriq (atezolizumab) combination therapy was well tolerated, resulted in stable disease as best response in 80% (8/10) of patients with advanced solid tumors (PMID: 31124055). 31124055
Unknown unknown Advanced Solid Tumor not applicable GDC-0919 Phase I Actionable In a Phase I trial, GDC-0919 (Navoximod) monotherapy was well tolerated, resulted in stable disease as best response in 50% (5/10) of patients with advanced solid tumors (PMID: 31124055). 31124055