Phase 1 Study of Epacadostat in Combination With Atezolizumab for Patients With Previously Treated Advanced Non-Small Cell Lung Cancer
Mené sur 29 patients atteints d'un cancer du poumon non à petites cellules de stade IIIB/IV, cet essai de phase I évalue la dose maximale tolérée de l'épacadostat (un inhibiteur de IDO1) et analyse ses caractéristiques pharmacocinétiques en combinaison avec l'atézolizumab, après l'échec d'une ou de plusieurs lignes de chimiothérapies à base de sels de platine
Epacadostat is a potent and highly selective inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1). Here we report results from the open-label, dose-escalation, phase 1b ECHO-110 study evaluating epacadostat plus atezolizumab in patients with previously treated stage IIIB/IV non-small cell lung cancer (NSCLC). Eligible patients had received ≥1 prior line of platinum-based chemotherapy (≥2 cycles) and no prior checkpoint/IDO inhibitors treatment. Oral epacadostat (25, 50, 75, 100, 200, or 300 mg) was administered twice daily (BID) with intravenous atezolizumab 1200 mg every 3 weeks (Q3W). Primary endpoints were safety, tolerability, and dose-limiting toxicities (DLTs). Twenty-nine patients received ≥1 dose of treatment. The maximum tolerated dose of epacadostat was not reached. Two patients had DLTs: 1 patient with grade 3 dehydration and hypotension (epacadostat 200 mg BID); 1 patient with grade 3 hyponatremia and grade 4 autoimmune encephalitis (epacadostat 300 mg BID). Twenty-three patients (79%) had treatment-related adverse events (AEs); 7 patients (24%) experienced grade 3/4 events; 5 patients (17%) discontinued treatment due to treatment-related AEs. No fatal treatment-related AEs occurred. One patient achieved a partial response (objective response rate, 3%), which was maintained for 8.3 months; 8 patients had stable disease. Baseline tumoral PD-L1 and IDO expression were low among patients with evaluable samples (1 of 23 expressed PD-L1; 5 of 17 expressed IDO). Epacadostat pharmacokinetics were comparable to historical controls. Epacadostat, at doses up to 300 mg BID, combined with atezolizumab 1200 mg Q3W was well tolerated in patients with previously treated NSCLC, although clinical activity was limited. This article is protected by copyright. All rights reserved.