Phase II trial of pembrolizumab and epacadostat in recurrent clear cell carcinoma of the ovary: An NRG oncology study GY016

Introduction. Early reports of PD-1 inhibition in ovarian clear cell carcinomas (OCCC) demonstrate promising response. We evaluated the combination of pembrolizumab and IDO -1 inhibitor epacadostat in patients with recurrent OCCC. Methods. This single arm, two-stage, phase 2 trial included those with measurable disease and 1-3 prior regimens. Patients received intravenous pembrolizumab 200 mg every 3 weeks and oral epacadostat 100 mg twice a day. Primary endpoint was overall response rate (ORR), secondary endpoints were toxicity, progression -free survival (PFS) and overall survival (OS). The study was powered to detect an absolute 25% increase in response (15% to 40%). Results. Between September 28, 2018 and April 10, 2019,14 patients enrolled at first stage. Rate of accrual was 2.3 patients per month. Median age was 65 years (44-89), 10 (71.4%) had >= 2 prior regimens. ORR was 21% (95% 5-51%) within 7 months of study entry with 3 partial responses, and 4 had stable disease (disease control rate 50%). Median PFS was 4.8 months (95% CI: 1.9-9.6), OS 18.9 months (95% CI: 1.9 -NR). Most common grade >= adverse events were electrolyte abnormalities and gastrointestinal pain, nausea, vomiting, bowel obstruction. July 2019, the study reached the pre-specified criteria to re-open to second stage; however, the study closed maturely in February 2021 due to insufficient drug supply. Conclusions. Pembrolizumab and epacadostat demonstrated an ORR of 21% in this small cohort of recurrent OCCC. The rapid rate of accrual highlights the enthusiasm and need for therapeutic studies in patients with (c) 2024 Elsevier Inc. All rights reserved.