David OMalley, Director of Translational and Clinical Research Partnerships; Leader, Clinical Trial Innovation at Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, shared on LinkedIn:
“Proud to share our phase I/II study of olaparib plus tremelimumab in women with recurrent BRCA1/2 mutated ovarian cancer, now published in Nature Communications.
This trial grew out of elegant preclinical science from Sarah Adams and colleagues. Their work showed that PARP inhibition synergizes with CTLA4 blockade in BRCA deficient ovarian cancer models, driven by sustained interferon gamma signaling in the tumor microenvironment. The clinical question was whether PARP inhibition could enhance tumor immunogenicity and promote antitumor immunity in our patients.We enrolled 50 women, and 60% of them had already received a PARP inhibitor.
Results:
- Overall response rate 32.7%, disease control rate 47.7%
- Disease control in 24% of PARPi exposed patients, a group not expected to benefit from olaparib alone
- Six patients with PFS beyond 12 months
- Low VSTM5 or IFIT1B expression in archival tumor associated with clinical benefit and improved PFS
The trial did not meet its prespecified efficacy endpoint, and the immune toxicity was real. Even so, we saw durable responses in a heavily pretreated, largely PARPi resistant population, and two candidate biomarkers were identified that can be measured in routinely available FFPE tissue.
Together, these findings tell us we are getting closer to unlocking immunotherapy for the right patients with ovarian cancer.
Thank you to Sarah Adams, Carolyn Muller, and the University of New Mexico team for leading this work. Thank you also to our collaborators at Moffitt, UVA, and Personalis, and to the research team at The James. Above all, thank you to the patients and families who made it possible.”
Title: Olaparib plus tremelimumab in women with recurrent ovarian cancer and a germline BRCA1 or BRCA2 mutation: a phase I/II study
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.
You can also read: OPTIMUM at ESMO 2026: Maintenance Olaparib With or Without Durvalumab in DDR-Mutated Advanced Biliary Tract Cancer
