Olaparib plus tremelimumab in women with recurrent ovarian cancer and a germline BRCA1 or BRCA2 mutation: a phase I/II study

In preclinical studies, poly(ADP-ribose) polymerase (PARP) inhibition 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 PARP inhibitor 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 a germline BRCA1 or BRCA2 mutation (NCT0257125).

Grade 3 or 4 non-hematologic toxicity was reported in 57% of subjects, with tremelimumab discontinuation in 34.7%. The overall response rate was 32.7% (95% CI 19.5-45.8%), with a disease control rate of 47.7% (95% CI 33.0-62.5%). In exploratory biomarker analyses, low VSTM5 or IFIT1B expression was associated with treatment benefit and progression-free survival (p<0.001).