Phase 2 trial of durvalumab and cediranib with or without olaparib in recurrent ovarian cancer

A phase 2 proof-of-concept study at the National Cancer Institute (Bethesda, MD) evaluated durvalumab, olaparib, and cediranib (D+O+C) and durvalumab plus cediranib (D+C) in patients with recurrent ovarian cancer. Sixty-eight patients were enrolled (39 in D+O+C; 29 in D+C). The primary endpoint was objective response rate (ORR). The ORR was 19.4% (95% CI 9.5-43.5) for D+O+C and 29.6% (13.8-46.9) for D+C; D+C met the primary endpoint while D+O+C did not. Median progression-free survival (PFS) was 4.5 months in both arms, with four exceptional responses (PFS ≥ 12 months) in both arms. Baseline tumors from exceptional responders and patients with clinical benefit (partial response or stable disease with PFS ≥ 4 months) demonstrated enrichment of immune activation and metabolic pathways, whereas tumors with no clinical benefit exhibited upregulation of vascular adaptation and cytoskeletal remodeling pathways. The author conclude that these findings support the proof-of-concept clinical activity of D+O+C and D+C and identify molecular signatures with potential predictive value in subsets of recurrent ovarian cancer.