Abstract PR004: Phase 2 study of the PD-L1 inhibitor durvalumab and VEGFR inhibitor cediranib combination with and without PARP inhibitor olaparib in patients with recurrent ovarian cancer

Abstract Preclinical data suggest increased DNA damage by PARP inhibitor (PARPi) may induce immunostimulatory micromilieu, thus enhance the efficacy of the immune checkpoint inhibitor and VEGF/VEGFR blockade combination. We conducted the proof-of-concept Phase 2 trial of the anti-PD-L1 antibody durvalumab (D) and VEGFR tyrosine kinase inhibitor cediranib (C) combination with and without PARPi olaparib (O) in recurrent ovarian cancer (rOC) (NCT02484404). Patients with high-grade serous (HGS) or clear cell (CC) rOC were eligible for the D+O+C cohort, and all histologies were eligible for the D+C cohort. Eligibility included RECIST v1.1 measurable disease, ECOG performance status 0–2, and adequate end-organ function and marrow function. Patients received D 1,500mg IV q 4 weeks and C 20mg QD (5 days on/2 days off) with or without O 300mg BID. Treatment continued until progression, unacceptable toxicity, or consent withdrawal. Primary endpoint was overall response rate (ORR). Secondary objectives were progression-free survival (PFS) and safety. RECIST response was evaluated every two cycles (q 8-9 weeks) and safety was assessed as a q1 cycle. Pre- and on-treatment biopsies and blood samples were collected for correlative studies. The data cutoff date is May 13, 2025. In the D+O+C cohort, 39 patients were enrolled [median of 3 prior treatment regimens (IQR 2–4), platinum-resistant or primary platinum-refractory rOC (84.6%), BRCA mutation positive (BRCAm; 15.4%), 34 HGS, 5 CC]. Three patients discontinued treatment during cycle 1–2 due to intercurrent illnesses (i.e., uncontrolled symptomatic ascites, pulmonary embolism with pneumonia, and ileus). Of 36 evaluable patients, ORR was 19.4% (7 PRs; 95% CI:8.2–36.0%). Median PFS was 4.5 months (mo)(95% CI:3.8–6.1 mo; with one ongoing responder with PR [17.9+ mo] and four exceptional responders [≥1 year]). In the D+C cohort, 29 patients were enrolled [median of 3 prior treatment regimens (IQR 2–5), platinum-resistant or primary platinum-refractory rOC (69.0%), BRCAm (10.3%), 21 HGS, 3 granulosa cell, 2 CC, 2 carcinosarcoma and 1 high-grade endometrioid]. Two patients discontinued treatment during cycle 1 due to acute stroke with uncontrolled hypertension (n=1) and bacterial peritonitis (n=1). Of 27 evaluable patients, ORR was 29.6% (8 PRs; 95% CI:13.8–50.2%). Median PFS was 4.5 mo (95% CI: 3.6–8.0 mo; with one ongoing responder with PR [24.0+ mo] and 4 exceptional responders [≥1 year]). The Grade 3/4 treatment-related adverse events occurring in ≥ 20% of patients included anemia (25.6%), lymphocyte count decreased (25.6%), and hypertension (20.5%) in the D+O+C arm, none were ≥ 20% in the D+C arm. No new safety signals were observed. Our data suggest that both D+O+C and D+C treatments show moderate efficacy in heavily-pretreated, platinum-resistant, non-BRCAm rOC patients. Ongoing translational analyses focus on elucidating biomarkers linked to treatment resistance. Citation Format: Junya Tabata, Tzu-Ting Huang, Elena Giudice, Kristen Ibanez, Jayakumar R. Nair, Kevin Conlon, Britanny Solarz, Valentina Bolanos, Stanley Lipkowitz, Bernadette Redd, Aanika Balaji. Warner, Jung-Min Lee. Phase 2 study of the PD-L1 inhibitor durvalumab and VEGFR inhibitor cediranib combination with and without PARP inhibitor olaparib in patients with recurrent ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl):Abstract nr PR004.