Olaparib plus tremelimumab in women with recurrent ovarian cancer and a germline BRCA1 or BRCA2 mutation: a phase I/II study
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: Response rates to immune checkpoint blockade (ICB) in ovarian cancer are low. In preclinical studies, poly(ADP-ribose) polymerase inhibition (PARPi) synergized with CTLA4 ICB to achieve long-term survival in Brca1-deficient ovarian cancer models. Here we evaluated the safety and efficacy of combined treatment with the PARPi olaparib and the CTLA4 ICB tremelimumab for recurrent epithelial ovarian cancer in a multi-site single-arm phase I/II study enrolling 50 women with germline BRCA1 or BRCA2 mutations (NCT02571725). In phase I, no new toxicities were identified (n = 3). In the combined phase I and II safety cohort (n = 49), 57% of subjects experienced grade 3 or 4 non-hematologic toxicity, with tremelimumab discontinuation in 34.7%. The primary phase II endpoint, overall response rate was 32.7% (95% CI 19.5-45.8%), and disease control rate was 47.7% (95% CI 33.0-62.5%). Secondary outcomes were progression-free survival (PFS, 3.0 months, 95% CI 2.7-5.9), and overall survival (24.3 months, CI 14.9-30.4). In exploratory post-hoc biomarker analyses, low VSTM5 or IFIT1B expression was associated with treatment benefit and improved PFS (p < 0.001). Although the trial did not meet its prespecified efficacy endpoint, PFS > 12 months in 6 subjects among this heavily pre-treated cohort highlight the need for biomarkers to select regimens for patients with recurrent ovarian cancer.
Source: Nature Communications
Authors: Sarah F. Adams, Phyllis A. Gimotty, Teresa L. Rutledge, David M. O’Malley, Kari Ring, Robert M. Wenham, Karen Finkelstein, Elizabeth Lokich, Daniel M. Falcon, Alyson Yeckes, Olufunmilola M. Oyebamiji, Kathryn J. Brayer, Eleanor Paskus, Nadja K. Falk, Ryland Richards, Ji-Hyun Lee, Steven C. Eberhardt, Dennis McCance, Xavier Paliard, Sean Boyle, Richard Chen, Huining Kang, Jose R. Conejo-Garcia, Olivier Rixe, Carolyn Y. Muller
Institutions: University of New Mexico, UNM Comprehensive Cancer Center, University of Pennsylvania, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, University of Virginia Cancer Center, University of Virginia, Moffitt Cancer Center, Southwest Women's Oncology, Brown University, Women & Infants Hospital of Rhode Island, Dartmouth–Hitchcock Medical Center, University of Florida Health, UF Health Cancer Center, Personalis (United States), Duke University, New Mexico Cancer Center, Daiichi Sankyo (United States)
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W7220942757