Study to evaluate the safety and efficacy of talazoparib, an oral PARP inhibitor, in combination with enzalutamide, an androgen receptor inhibitor.
Investigators have administered the first dose in the phase 3 TALAPRO-3 study of talazoparib and enzalutamide in patients with metastatic castration-sensitive prostate cancer (mCSPC), according to a press release from Pfizer.
The study is evaluating the safety and efficacy of talazoparib, an oral poly ADP ribose polymerase (PARP) inhibitor, in combination with enzalutamide, an androgen receptor inhibitor. These findings are being compared with placebo plus enzalutamide in men with DNA damage response (DDR)-deficient mCSPC.
“The prognosis for men with advanced prostate cancer has significantly improved since the introduction of novel hormone therapies, but additional therapeutic options are needed for the approximately 25% of men with tumors harboring DNA damage response gene mutations, who may have poorer outcomes,” said Chris Boshoff, MD, PhD, chief development officer of oncology at Pfizer Global Product Development, in a press release.
The trial will enroll approximately 500 men across 285 clinical trial sites in 28 countries, with a primary endpoint of radiographic progression-free survival (rPFS) and a secondary endpoint of overall survival (OS).
“By combining enzalutamide, which has a proven clinical benefit in men with metastatic castration-sensitive prostate cancer, with talazoparib, our PARP inhibitor that is active in DDR-mutated cancer, we may be able to offer a new treatment option that targets the underlying genetic mechanisms associated with DDR-mutated mCSPC,” Boshoff said in the press release.
Talazoparib is currently approved for the treatment of adults with deleterious or suspected deleterious germline BRCA-mutated human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, according to the press release. Enzalutamide is an androgen receptor inhibitor currently approved for the treatment of patients with castration-resistant prostate cancer and mCSPC.
Patients in the TALAPRO-3 trial will be randomly assigned to receive either talazoparib 0.50 mg once daily in combination with enzalutamide 160 mg once daily or placebo capsules. Men with renal impairment at screening may be enrolled and given a lower dose of either talazoparib or the placebo.
“With the introduction of PARP inhibitors in the metastatic castration-resistant prostate cancer setting, it is important to explore how a combination approach may impact outcomes for men with metastatic castration-sensitive disease,” said Neeraj Agarwal, MD, senior director of clinical research innovation at the Huntsman Cancer Institute and member of the TALAPRO-3 steering committee, in the press release. “It’s exciting to be at the forefront of landmark studies like TALAPRO-3, which are helping to further our understanding of how different approaches may advance care for these men.”
First Participant Dosed in Pfizer’s Pivotal Phase 3 TALAPRO-3 Combination Study of Talazoparib and Enzalutamide in Metastatic Castration-Sensitive Prostate Cancer (mCSPC). News release. Pfizer. June 23, 2021. Accessed June 29, 2021. https://www.pfizer.com/news/press-release/press-release-detail/first-participant-dosed-pfizers-pivotal-phase-3-talapro-3