OBJECTIVE: PARP inhibitors may work synergistically to improve the efficacy of immunotherapy in patients with epithelial ovarian cancer (EOC). We performed a parallel-arm study of tremelimumab, alone or with olaparib, in patients with recurrent EOC. METHODS: Eligibility criteria included measurable disease and progression <
12 months from last platinum. Participants were randomized to Arm A (tremelimumab monotherapy, 10 mg/kg/dose intravenously [IV]) or Arm B (dose level 1 [DL1] olaparib orally 150 mg twice daily with tremelimumab IV 3 mg/kg/dose and DL2 olaparib orally 150 mg twice daily with tremelimumab IV 10 mg/kg/dose). Primary objectives were safety, change in peripheral ICOS RESULTS: Among 24 total patients (12 on Arm A, 6 on Arm B-DL1, 6 on Arm B-DL2), the most common grade 3 toxicities were rash (13 %), immune-mediated hepatitis (8 %), and colitis (8 %). No grade ≥ 4 toxicities were identified. No dose-limiting toxicities were identified. One patient (Arm B-DL2) experienced a partial response
no complete responses were observed. Ten patients (7 on Arm A, 2 on Arm B-DL2, and 1 on Arm B-DL1) had a best response of stable disease. There was a significant increase in CD4 CONCLUSIONS: Tremelimumab IV 10 mg/kg/dose with olaparib 150 mg orally twice daily was safe and feasible. Tremelimumab 10 mg/kg/dose (as opposed to 3 mg/kg/dose) was required for immune activation, although this did not translate into clinical responses.