FDA Grants Priority Review to New Drug Application for Talazoparib, Enzalutamide in mCRPC


Positive data on the novel prostate cancer combination treatment was presented at the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium.

The FDA has granted priority review to a supplemental new drug application (sNDA) for the combination of talazoparib (Talzenna; Pfizer) and enzalutamide (Xtandi; Pfizer) for metastatic castration-resistant prostate cancer (mCRPC). The combination showed significantly improved radiographic progression-free survival (rPFS) compared to placebo and enzalutamide, according to positive results from the phase 3 TALAPRO-2 study presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium 2023.

Talazoparib with enzalutamide reduced the risk of disease progression or death by 37% compared to placebo and enzalutamide. Additionally, it showed improvement in men with or without homologous recombination repair (HRR) gene mutation.

“The results from the TALAPRO-2 study show that the addition of talazoparib to the existing standard of care adds significant clinical benefit,” said lead investigator Neeraj Agarwal, MD, FASCO, professor of Oncology and Presidential Endowed Chair of Cancer Research at Huntsman Cancer Institute, University of Utah, in a press release. “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 mutation.”

Talazoparib is an oral poly ADP-ribose polymerase (PARP) inhibitor that can repair damaged DNA by trapping PARPs at sites of DNA damage to prevent cancer cell growth. Preclinical studies found that a PARP inhibitor’s anti-tumor effect could be strengthened when combined with an androgen receptor signaling inhibitor (ARSi), such as enzalutamide.

Investigators conducted the phase 3, 2-part, 2-cohort, multicenter, randomized, double-blind, and placebo-controlled TALAPRO-2 study to evaluate the safety and efficacy of talazoparib with enzalutamide. The primary endpoint was rPFS, or the time from randomization to evidence of radiographic cancer progression or death. Secondary endpoints were overall survival (OS), objective response rate (ORR), response duration, and prostate-specific antigen (PSA) response.

The team enrolled more than 1000 patients with mCRPC globally. The 2 cohorts included all-comers and patients with HRR mutations, who were randomized to receive talazoparib and enzalutamide or enzalutamide with placebo. The experimental arm did not reach median rPFS, positively showing that fewer participants experienced disease progression or death. Additionally, OS improved in the talazoparib arm compared to the control, and ORR and time to PSA progression improved as well.

The most common adverse events (AEs) were anemia (65.8%), reduced neutrophil count (35.7%), fatigue (33.7), reduced platelet count (24.6%), back pain, reduced white blood cell count (22.1% each), and reduced appetite (21.6%).

mCRPC is cancer that has progressed to other parts of the body despite medical or surgical testosterone-lowering treatment. As much as 20% of prostate cancer cases become mCRPC within 5 to 7 years of diagnosis, and cases were numbered at 3 million in the United States in 2020.

“Patients with mCRPC need new treatment approaches that can improve outcomes, and the rPFS results from TALAPRO-2…demonstrate the potential of the talazoparib and enzalutamide combination, if approved, to become a new standard of care,” said Chris Boshoff, MD, PhD, chief development officer, Oncology and Rare Disease, Pfizer Global Product Development, in the press release.


Pfizer. Pfizer Announces Positive TALZENNA® and XTANDI® Combination Data from Phase 3 TALAPRO-2 Study. News Release. February 16, 2023. Accessed February 21, 2023. https://www.businesswire.com/news/home/20230216005496/en

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