atezolizumab + epacadostat

The combination of atezolizumab + epacadostat is an investigational cancer treatment that combines two distinct mechanisms of action. Atezolizumab is a PD-L1 inhibitor (immune checkpoint inhibitor), while epacadostat is a potent and highly selective IDO1 (indoleamine 2,3-dioxygenase 1) inhibitor[1][2]. This combination was studied primarily in patients with previously treated advanced or metastatic non-small cell lung cancer (NSCLC) and urothelial carcinoma[3]. ## Clinical Development The combination was evaluated in a Phase 1b clinical trial called ECHO-110, which assessed the safety, tolerability, and preliminary efficacy of epacadostat administered with atezolizumab in patients with previously treated Stage IIIB/IV NSCLC[1][2]. In this study: - Oral epacadostat was administered at various doses (25, 50, 75, 100, 200, or 300 mg) twice daily (BID) - Intravenous atezolizumab was given at 1,200 mg every 3 weeks (Q3W) - The primary endpoints were safety, tolerability, and dose-limiting toxicities (DLTs)[1] Twenty-ninety patients received at least one dose of the treatment combination. The maximum tolerated dose of epacadostat was not reached during the study[1]. Two patients experienced dose-limiting toxicities: one with Grade 3 dehydration and hypotension (at epacadostat 200 mg BID) and another with Grade 3 hyponatremia and Grade 4 autoimmune encephalitis (at epacadostat 300 mg BID)[1][2]. ## Safety Profile The combination was generally well-tolerated: - 79% of patients (23/29) experienced treatment-related adverse events - 24% (7 patients) had Grade 3/4 events - 17% (5 patients) discontinued treatment due to treatment-related adverse events - No fatal treatment-related adverse events occurred[1][2] ## Efficacy Results Clinical activity of the combination appeared limited: - Only one patient achieved a partial response (objective response rate of 3%), which lasted for 8.3 months - Eight 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)[1][2] The pharmacokinetics of epacadostat in this combination was comparable to historical controls[1]. While the combination demonstrated acceptable tolerability at doses up to 300 mg BID of epacadostat with atezolizumab 1,200 mg Q3W, the limited clinical activity observed suggests this particular combination may not provide significant therapeutic advantage in the studied patient population.