Multicenter phase 1-2 study of olaparib plus tremelimumab in women with recurrent ovarian cancer and a germline BRCA1/2 mutation

Response rates to immune checkpoint blockade ICB) in ovarian cancer are low. In preclinical ovarian cancer models, PARP inhibitors synergized with CTLA4 ICB. A multicenter phase 1-2 study investigated safety and efficacy of combined treatment with olaparib and tremelimumab for recurrent epithelial ovarian cancer I women with germline BRCA1 or BRCA2 mutations. In phase 1 (n=3), no new toxicities were identified. In the combined phase 1 and 2 safety cohort (n=49), 57% of subjects experienced grade 3 or 4 non-hematologic toxicity, with tremelimumab discontinuation in 34.7%. The primary phase 2 endpoint, overall response rate was 32.7% (95% CI 19.5-45.8) and disease control rate was 47.7% (33.0-62.5). Secondary outcomes were progression-free survival (3.0 months; 95% CI 2,7-5.9) and overall survival (24.3 months; 14.9-30.4). In explaratory post-hoc biomarker analysis, low VSTM5 or IFIT1B expression was associated with treatment benefit and improved progression-free survival (p<0.001). The authors conclude that, although the trial did not meet its prespecified efficacy endpoint, progression-free survival longer than 12 months in 6 subjects among this heavily pretreated cohort highlights the need for biomarkers to select regimens for patients with recurrent ovarian cancer.