ECHO-202/KEYNOTE-037 is an ongoing open-label, phase I/II study evaluating epacadostat + pembrolizumab in multiple tumor types. For this analysis, eligible patients had (i) advanced clear-cell RCC, (ii) prior antiangiogenic therapy, and (iii) no prior checkpoint inhibitor therapy. In the phase I portion of the trial, patients received dose escalation epacadostat (25, 50, 100, or 300 mg PO BID) + pembrolizumab (2 mg/kg or 200 mg IV Q3W). For the phase II trial, 100 mg BID epacadostat + 200mg Q3W pembrolizumab was selected for treatment. Response rate was assessed using the RECIST 1.1 criteria and tolerability was assessed in patients receiving ≥1 epacadostat + pembrolizumab dose. There were 33 patients (phase I – n=11, phase II – n=22) enrolled in the trial, with a median age of 63 years, 70% of patients were male, and majority were Caucasian (97%). There were 6% of patients with favorable MSKCC criteria, 64% were intermediate, and 12% of patients were poor criteria. Among 30 patients with evaluable data, 63% had 0-1 and 37% had ≥2 prior therapies, respectively. Among patients with 0-1 prior therapies, the objective response rate (ORR) was 47% and disease control rate (DCR) was 58%. Among patients with ≥2 prior therapies, ORR was 0% and DCR was 36%. At the time of analysis, all patients demonstrating a treatment response were still ongoing (range: 1-372 days). Adverse events occurred in 10% of patients, including fatigue, rash, arthralgia, diarrhea, pruritus, and pyrexia.
In conclusion, epacadostat + pembrolizumab was generally well tolerated, with encouraging outcomes in these high-risk patients with failed prior therapy. Given the dismal outcomes for these patients with prior failed therapy, novel clinical trials demonstrating improved PFS and OS are desperately needed. A phase III trial is planned and we look forward to these results.
Clinical trial: NCT02178722
Presented By: Primo Lara, University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA
Co-Authors: Todd Michael Bauer, Omid Hamid, David C. Smith, Thomas Gajewski, Tara C. Gangadhar, Bradley G. Somer, Emmett V. Schmidt, Yufan Zhao, Hema Gowda, Anthony J. Olszanski
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA