A clinical study of tremelimumab, alone or in combination with olaparib, for recurrent epithelial ovarian cancer

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⁺ T cells, and identification of optimal dose combination. 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⁺ICOS⁺ and CD8⁺ICOS⁺ T cells at both C1D15 and C1D22 in groups treated with tremelimumab IV 10 mg/kg/dose, but not in those treated with tremelimumab 3 mg/kg/dose. 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.