Phase Ii Study Of Olaparib (O) Plus Durvalumab (D) And Bevacizumab (B) (Mediola): Initial Results In Patients (Pts) With Non-Germline Brca-Mutated (Non-Gbrcam) Platinum Sensitive Relapsed (Psr) Ovarian Cancer (Oc)

Olaparib is a PARP inhibitor approved in first-line and recurrent OC. Results of O+D in gBRCAm PSR OC have been presented. MEDIOLA (NCT02734004) then evaluated combining O+D (doublet cohort) or O+D+B (triplet cohort) in non-gBRCAm PSR OC. Here we present initial results. Pts had confirmed non-gBRCAm PSR OC and had progressed after receiving 1–2 prior lines (L) of platinum-based chemotherapy. Pts received O 300 mg bid and D 1.5g IV q4 weeks (w) and B 10 mg/kg q2w (triplet only) until progressive disease. Tumours were assessed by RECIST v1.1 at baseline and q8w. Primary endpoints were safety and 24-w disease control rate (DCR). Secondary endpoints included objective response rate (ORR), median duration of response (mDOR) and progression-free survival (PFS). From Nov 2018 to Feb 2019, 32 pts (69% 2nd L) enrolled and received O+D; from May 2018 to Jan 2019, 31 (68% 2nd L) enrolled and received O+D+B. At the data cut-off 13 Feb 2020, 22% of O+D and 42% of O+D+B pts remained on treatment. The most common grade ≥3 AEs in O+D were anaemia, lipase increased and neutropenia and anaemia, hypertension, fatigue, lipase increased, and neutropenia in O+D+B. Two (6%) and five (16%) pts discontinued one or more study drug due to an AE in O+D and O+D+B, respectively. Efficacy is summarized in the table. Efficacy in biomarker subgroups, including by presence of genome-wide loss of heterozygosity, will be presented.Table:Non-gBRCAm PSR OCDoublet cohort (O+D) n=32Triplet cohort (O+D+B) n=3124-w DCR, %28.1% (90% CI 15.5–43.9)77.4% (90% CI 61.7–88.9)Confirmed ORR, %31.3% (95% CI 16.1–50.0)77.4% (95% CI 58.9–90.4)Median confirmed DOR (mo)6.9 (IQR 5.7–11.1)11.1 (IQR 9.0–16.4)Median PFS (mo)5.5 (95% CI 3.6–7.5)14.7 (95% CI 10.0–18.1)CI, confidence interval; IQR, interquartile range. Open table in a new tab CI, confidence interval; IQR, interquartile range. Combining O+D and O+D+B was well tolerated in pts with non-gBRCAm PSR OC, consistent with the known safety profiles of the single agents. The DCR for the doublet cohort did not meet the prespecified target of 80%. The 95% CI for DCR in the triplet cohort included the prespecified target of 80%. ORR and PFS in the triplet cohort demonstrate promising activity in non-gBRCAm PSR OC, and in this group the ORR and PFS are higher than reported for single-agent PARP or VEGF inhibitors.