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 (18Suppl): Abstract nr PR004.
Tabata et al. (Fri,) studied this question.