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The first patient has been dosed in the phase 3 TALAPRO-3 study evaluating the combination of the PARP inhibitor talazoparib and the antiandrogen agent enzalutamide (Xtandi) in patients with DNA damage response (DDR)-deficient metastatic castration-sensitive prostate cancer (mCSPC).1
The global, double-blind TALAPRO-3 trial will randomize approximately 550 men to enzalutamide plus either talazoparib or placebo. The study is being conducted at nearly 300 clinical sites spanning 28 countries. The initial patient dose was administered at a study location in Glendale, California.
“With the introduction of PARP inhibitors in the metastatic castration-resistant prostate cancer (mCRPC) setting, it is important to explore how a combination approach may impact outcomes for men with metastatic castration-sensitive disease,” Neeraj Agarwal, MD, professor of Oncology at the University of Utah School of Medicine, senior director for Clinical Research Innovation at Huntsman Cancer Institute, and member of the TALAPRO-3 steering committee, stated in a 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.”
To enroll on the trial, patients must have an ECOG performance status of 0 to 1 and confirmed DDR mutation status through liquid biopsy and/or de novo or archival tumor tissue. Prior therapy is allowed. Patients with brain metastases are not eligible for enrollment. Radiographic progression-free survival is the primary end point of the study, and overall survival is a secondary end point. The estimated primary completion date for the trial is the end of 2024.
“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 percent of men with tumors harboring DDR gene mutations, who may have poorer outcomes,” Chris Boshoff, MD, PhD, chief development officer, Oncology, Pfizer Global Product Development, stated in the press release. “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.”
Beyond TALAPRO-3, the combination of talazoparib and enzalutamide is also being explored in the ongoing phase 3 randomized, double-blind, placebo-controlled TALAPRO-2 trial in patients with mCRPC. DDR defects are not required to enroll.
Enzalutamide has FDA-approved indications for the treatment of patients with mCSPC and mCRPC.
Talazoparib does not have an FDA approval in prostate cancer. The PARP inhibitor is currently approved by the FDA for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated, HER2‑negative locally advanced or metastatic breast cancer.
There are currently 2 PARP inhibitors—rucaparib (Rubraca) and olaparib (Lynparza)—approved in the prostate cancer space, both for the treatment of patients with metastatic castration-resistant disease.
1. First Participant Dosed In Pfizer’s Pivotal Phase 3 Talapro-3 Combination Study Of Talazoparib And Enzalutamide In Metastatic Castration-Sensitive Prostate Cancer (MCSPC). Published online June 23, 2021. Accessed June 23, 2021. https://bit.ly/3gVirn3