ECHO-202/KEYNOTE-037 is an open-label, phase I/II study of Epac + Pembro in patients with advanced tumors (Clinical trial information: NCT02178722). Dr. Smith presented data from the phase I/II efficacy and safety outcomes for the UC cohort.
Patients included in this study were with advanced UC, prior platinum therapy (adjuvant or advanced disease setting) or alternative therapy (if platinum was not appropriate), and no prior checkpoint inhibitor therapy. In phase I, patients received Epac (25, 50, 100, or 300 mg PO BID) + Pembro (2 mg/kg or 200 mg IV Q3W). At all points the maximal tolerated dose was not exceeded. For the phase II trial Epac (100 mg BID) + Pembro (200 mg Q3W) dosing was selected. Response was assessed in RECIST 1.1–evaluable patients. Safety was assessed in patients receiving ≥1 Epac + Pembro dose.
Overall, a total of 40 pts (phase I, n = 5; phase II, n = 35) were evaluated. Median age was 67 years, 75% were men, 88% were white, 100% had prior platinum therapy, and 75% had 0–1 prior line of therapy for advanced disease. Out of the 40 patients 2 completed it, 11 are ongoing and 27 discontinued it. Median follow-up was 33.8 weeks (range 3.6-131). Preliminary objective response rate (ORR) (Complete response [CR] and partial response [PR]) and durable complete response (DCR) (CR+PR+SD) for all efficacy-evaluable patients were 35% and 53%, respectively. For pts with 0–1 prior line of therapy for advanced disease, ORR and DCR were 38% and 59%. The most common adverse events (AE) were fatigue (33%), rash (20%), and increased amylase levels (13%; asymptomatic). Grade ≥3 AE occurred in 23% of patients. No treatment related deaths had occurred.
To conclude, Epac + Pembro was generally well tolerated and associated with increased response compared with previously reported PD-1 inhibitor monotherapy in patients with advanced UC. The efficacy of Epac + Pembro in UC patients with 0-1 prior lines of therapy supports phase III investigation of this combination.
Presented By: David C. Smith, University of Michigan, Ann Arbor, MI
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA