Safety of epacadostat 100 mg bid plus pembrolizumab 200 mg Q3W in advanced solid tumors: Phase 2 data from ECHO-202/KEYNOTE-037.

3012 Background: The immunosuppressive enzyme indoleamine 2, 3-dioxygenase 1 (IDO1) facilitates immune tolerance in cancer via T-cell suppression, and IDO1 overexpression is associated with poor survival. Epacadostat, an oral inhibitor of IDO1, has been shown to be well tolerated as monotherapy and in combination with checkpoint inhibitors. ECHO-202/KEYNOTE-037 is a phase 1/2 study evaluating the safety and efficacy of oral epacadostat plus IV pembrolizumab in patients (pts) with advanced tumors. Based on phase 1 outcomes, epacadostat 100 mg BID plus pembrolizumab 200 mg Q3W was selected for phase 2 evaluation. This analysis summarizes phase 2 safety experience in the overall population of ECHO-202/KEYNOTE-037 (pooled across tumor types) at an October 29, 2016 data cutoff. Methods: Phase 2 pts were ≥18 years of age with advanced or recurrent melanoma (MEL), non–small cell lung cancer (NSCLC), renal cell carcinoma (RCC), urothelial carcinoma (UC), triple-negative breast cancer, squamous cell carcinoma of head and neck (SCCHN), ovarian cancer, diffuse large B-cell lymphoma, or microsatellite instability–high colorectal cancer. Results: The overall safety population comprised 244 pts receiving ≥1 study treatment dose. Median age was 63 years, 52% were women, and 91% were white. As of data cutoff, 134 study pts (55%) discontinued study treatment, primarily due to disease progression (n = 97). Median exposure to study treatment was 86 days (range, 1–374 days). TRAEs occurring in ≥5% of pts were fatigue (23%); rash (16%); diarrhea and nausea (7% each); increased alanine aminotransferase, increased aspartate aminotransferase, and pruritus (6% each); and pyrexia (5%). A total of 37 pts (15%) had grade ≥3 TRAEs; the most common grade ≥3 TRAEs were increased lipase (asymptomatic) and rash (3% each). TRAEs led to discontinuation in 3% of pts. Conclusions: Epacadostat 100 mg BID plus pembrolizumab 200 mg Q3W was associated with an acceptable safety profile in pts with advanced cancers, supporting continued evaluation of the combination. The phase 3 ECHO-301/KEYNOTE-252 MEL study is ongoing and additional phase 3 studies (NSCLC, UC, RCC, SCCHN) are planned. Clinical trial information: NCT02178722.