TY - JOUR
T1 - A Phase Ib, Open-label Study Evaluating the Safety and Efficacy of Ipatasertib plus Rucaparib in Patients with Metastatic Castration-resistant Prostate Cancer
AU - Pook, David
AU - Geynisman, Daniel M.
AU - Carles, Joan
AU - de Braud, Filippo
AU - Joshua, Anthony M.
AU - Pérez-Gracia, José Luis
AU - Pérez, Casilda Llácer
AU - Shin, Sang Joon
AU - Fang, Bruno
AU - Barve, Minal
AU - Maruzzo, Marco
AU - Bracarda, Sergio
AU - Kim, Miso
AU - Kerloeguen, Yannick
AU - Gallo, Jorge Daniel
AU - Maund, Sophia L.
AU - Harris, Adam
AU - Huang, Kuan Chieh
AU - Poon, Victor
AU - Sutaria, Dhruvitkumar S.
AU - Gurney, Howard
N1 - Funding Information:
The study was funded by F. Hoffmann-La Roche and Genentech, a member of the Roche group. We thank the patients who participated in the trial and the clinical site investigators. We thank Andrea Loehr and Heidi Giordano of Clovis Oncology for their contributions to the study. We thank Kenta Yoshida and Rucha Sane for assistance with pharmacokinetic study design and analysis. Medical writing assistance for this manuscript was provided by Scott Battle, PhD (Health Interactions), funded by F. Hoffmann-La Roche.
Publisher Copyright:
© 2023 American Association for Cancer Research.
PY - 2023/9/1
Y1 - 2023/9/1
N2 - 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 400mgdaily) 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.
AB - 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 400mgdaily) 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.
UR - http://www.scopus.com/inward/record.url?scp=85171526758&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-22-2585
DO - 10.1158/1078-0432.CCR-22-2585
M3 - Article
C2 - 37339186
AN - SCOPUS:85171526758
SN - 1557-3265
VL - 29
SP - 3292
EP - 3300
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 17
ER -