Pfizer announced positive results from the Phase 3 TALAPRO-2 study of TALZENNA (talazoparib), an oral poly ADP-ribose polymerase (PARP) inhibitor, in combination with XTANDI (enzalutamide), demonstrating a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) compared to placebo plus XTANDI in men with metastatic castration-resistant prostate cancer (mCRPC), with or without homologous recombination repair (HRR) gene mutations.

In addition, the U.S. Food and Drug Administration (FDA) has granted Priority Review for Pfizer’s supplemental new drug application (sNDA) for TALZENNA in combination with XTANDI for the treatment of men with mCRPC. The FDA grants Priority Review to medicines that may offer significant advances in treatment or may provide a treatment where no adequate therapy exists. The FDA’s decision on the sNDA is expected in 2023.

“Novel hormone therapies dramatically changed outcomes for patients with mCRPC in the last decade, and the results from the TALAPRO-2 study show that the addition of talazoparib to the existing standard of care adds significant clinical benefit,” said Neeraj Agarwal, M.D., FASCO, Professor of Oncology and Presidential Endowed Chair of Cancer Research at Huntsman Cancer Institute, University of Utah, and lead investigator for TALAPRO-2. “In addition to delaying disease progression, this combination delayed prostate-specific antigen progression and time to chemotherapy without adversely impacting patient quality of life. The TALAPRO-2 results support the potential for this combination to be practice-changing, with strong, highly consistent efficacy and observations in mCRPC patients both with or without HRR gene mutations, and across clinically relevant sub-populations.”

A trend in overall survival (OS) favoring TALZENNA plus XTANDI was also observed, though these data are immature. The final OS will be reported once the predefined number of survival events has been reached. TALAPRO-2 is the first Phase 3 study to combine TALZENNA with XTANDI in patients unselected for genetic alterations in DNA damage repair pathways, directly or indirectly involved with HRR.

“Patients with mCRPC need new treatment approaches that can improve outcomes, and the rPFS results from TALAPRO-2, which appears to be the longest observed in a randomized trial in this setting, demonstrate the potential of the TALZENNA and XTANDI combination, if approved, to become a new standard of care,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology and Rare Disease, Pfizer Global Product Development. “We are pleased that the FDA has granted Priority Review for our application, and we look forward to working with the Agency and global regulatory authorities to bring this treatment to men with mCRPC.”