Scientific publications
A Phase Ib, Open-label Study Evaluating the Safety and Efficacy of Ipatasertib plus Rucaparib in Patients with Metastatic Castration-resistant Prostate Cancer. Scientific Publication
David Pook 1 , Daniel M Geynisman 2 , Joan Carles 3 , Filippo de Braud 4 , Anthony M Joshua 5 , José Luis Pérez-Gracia 6 , Casilda Llácer Pérez 7 , Sang Joon Shin 8 , Bruno Fang 9 , Minal Barve 10 , Marco Maruzzo 11 , Sergio Bracarda 12 , Miso Kim 13 , Yannick Kerloeguen 14 , Jorge Daniel Gallo 14 , Sophia L Maund 15 , Adam Harris 15 , Kuan-Chieh Huang 15 , Victor Poon 15 , Dhruvitkumar S Sutaria 15 , Howard Gurney 16
Purpose: To report the safety and efficacy of ipatasertib (AKT inhibitor) combined with rucaparib (PARP inhibitor) in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with second-generation androgen receptor inhibitors.
Patients and methods: In this two-part phase Ib trial (NCT03840200), patients with advanced prostate, breast, or ovarian cancer received ipatasertib (300 or 400 mg daily) plus rucaparib (400 or 600 mg twice daily) to assess safety and identify a recommended phase II dose (RP2D). A part 1 dose-escalation phase was followed by a part 2 dose-expansion phase in which only patients with mCRPC received the RP2D. The primary efficacy endpoint was prostate-specific antigen (PSA) response (≥50% reduction) in patients with mCRPC. Patients were not selected on the basis of tumor mutational status.
Results: Fifty-one patients were enrolled (part 1 = 21; part 2 = 30). Ipatasertib 400 mg daily plus rucaparib 400 mg twice daily was the selected RP2D, received by 37 patients with mCRPC. Grade 3/4 adverse events occurred in 46% (17/37) of patients, with one grade 4 adverse event (anemia, deemed related to rucaparib) and no deaths. Adverse events leading to treatment modification occurred in 70% (26/37). The PSA response rate was 26% (9/35), and the objective response rate per Response Criteria in Solid Tumors (RECIST) 1.1 was 10% (2/21). Median radiographic progression-free survival per Prostate Cancer Working Group 3 criteria was 5.8 months [95% confidence interval (CI), 4.0-8.1], and median overall survival was 13.3 months (95% CI, 10.9-not evaluable).
Conclusions: Ipatasertib plus rucaparib was manageable with dose modification but did not demonstrate synergistic or additive antitumor activity in previously treated patients with mCRPC.
CITATION Clin Cancer Res. 2023 Sep 1;29(17):3292-3300. doi: 10.1158/1078-0432.CCR-22-2585
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