Durvalumab versus physician's choice chemotherapy in recurrent ovarian clear cell adenocarcinoma (MOCCA/APGOT-OV2/GCGS-OV3): a multicenter, randomized, phase 2 trial.

PURPOSE The optimal treatment of recurrent ovarian clear cell carcinoma (rOCCC) remains unknown. This is the first randomized trial to compare durvalumab with chemotherapy in rOCCC. PATIENTS AND METHODS MOCCA is a randomized, phase 2 trial conducted in Singapore, Korea and Australia. Eligible patients had rOCCC with recurrence after platinum-based chemotherapy, ECOG performance status ≤2 and no prior immune checkpoint blockade. Patients were randomly assigned (2:1) to durvalumab (1500mg every 4 weeks) or chemotherapy. Patients progressing on chemotherapy were allowed to crossover to durvalumab. The primary outcome was progression-free survival (PFS). Secondary outcomes included overall survival (OS), objective response rates (ORR), and safety. RESULTS 48 eligible women were assigned to durvalumab (N= 31) or chemotherapy (N= 17). Median PFS was 7.6 (95% CI 7.0-16.0) and 14.0 (95% CI 7.0-32.9) weeks with durvalumab or chemotherapy, (HR 1.6, 95% CI 0.8-3.0; P= 0.92). Median OS was 37.9 (95% CI 21.7-143.0) and 40.6 (95% CI 25.0-not reached) weeks, respectively (HR 1.5, 95% CI 0.7-3.3; P= 0.85). The difference in ORR between groups was not statistically significant (durvalumab 9.7% vs PCC 18.8%; difference -9.1%, 95% CI -31.3%-12.9%; P= 0.83). Fewer all-grade (35.5% vs 68.8%) and high-grade (9.7% vs 31.3%) treatment-related adverse events were observed for durvalumab. PD-L1 CPS+ was observed in 28.9% (CPS≥1%) and 10.5% (CPS≥10%) of patients. PIK3CA mutations were associated with time to progression on durvalumab ³12 weeks (RR(-mutated vs -wildtype) 2.83, 95% CI 1.16 to 14.17). CONCLUSIONS Durvalumab was well-tolerated, but did not improve efficacy outcomes compared with chemotherapy in rOCCC.