DORA: A Phase II, Multicenter, International, Non-Comparator Study of Olaparib (O) plus /- Durvalumab (D) as a chemotherapy-free maintenance strategy in Platinum tReated Advanced Triple-Negative Breast Cancer (aTNBC)

Abstract Introduction: A significant proportion of aTNBC patients carry homologous recombination defects associated with platinum sensitivity. Olaparib is an approved PARP inhibitor (PARPi) for germline BRCA (gBRCA) associated early and metastatic breast cancer as well as maintenance therapy in platinum-sensitive ovarian cancer irrespective of gBRCA status. PARPi enhances immune response via cGAS/STING activation and is synergistic with anti-PD-1 blockade in preclinical models without overlapping toxicities. Here, the efficacy of maintenance olaparib (O) +/- durvalumab (D) in aTNBC patients following clinical benefit from platinum chemotherapy is investigated (NCT03167619). Methods: Eligible pts had aTNBC with investigator-assessed clinical benefit (SD, PR, CR) after a minimum of 3 q3-weekly or 6 q1-weekly cycles of platinum-based chemotherapy in the 1st or 2nd line treatment setting. Patients were randomized 1:1 to receive O 300 mg BID daily or O 300mg BID daily + D 1.5g IV q4 wks. The study was a non-comparator trial; randomization aimed to reduce bias. Tumors were evaluated by RECIST1.1 at baseline and q8 wks. Known gBRCA carriers were limited to 10. The primary endpoint was progression-free survival (PFS). Secondary endpoints were disease control rate (DCR), clinical benefit rate (CBR), and overall survival (OS). Results: From 2/4/2019-12/24/2020, 45 pts were randomized (23 pts in O arm; 22 in O+D arm). 82.2% received platinum as 1st line therapy and 82% received a platinum-doublet. As of data cutoff (6/30/2021), median follow-up of 9.8m (7.2-15.1), the median PFS was 3.95m (p= 0.0023; 95% CI 2.55-6.13) with O monotherapy. The median PFS was 6.1 mos (p= <.0001; 95% CI 3.68-10.11) in the O+D arm. CBR (CR, PR or SD ≥ 24 wks) was 39.1% (19.7%-61.5%) and 36.4% (17.2%-59.3%) in the O and O+D arms, respectively. DCR was 52.2% (30.6%, 73.2%) and 68.2% (45.1%, 86.1%) in the O and O + D arms, respectively. Currently, 7 pts (15.6%) remain on study treatment, only 2 have gBRCA alterations. No new safety signals were reported. Correlative analysis including germline/somatic BRCA, HRR genes, BRCA methylation, TMB and PDL-1 in association with clinical outcomes will be presented. Conclusions: A subset of non-gBRCA altered aTNBC pts who derived clinical benefit from platinum-based chemotherapy had a durable disease control with a chemotherapy-free maintenance strategy of olaparib +/- durvalumab. Citation Format: Sarah L. Sammons, Tira J. Tan, Young Hyunk Im, Tiffany A. Traina, Carey Anders, Ezekiel Renzulli, Sung-Bae Kim, Rebecca Dent. PD11-12 DORA: A Phase II, Multicenter, International, Non-Comparator Study of Olaparib (O) +/- Durvalumab (D) as a chemotherapy-free maintenance strategy in Platinum tReated Advanced Triple-Negative Breast Cancer (aTNBC) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD11-12.