On July 22, 2026, Pfizer announced that the US Food and Drug Administration (FDA) accepted for Priority Review a supplemental New Drug Application for talazoparib plus enzalutamide in men with homologous recombination repair gene-altered metastatic castration-sensitive prostate cancer.
The FDA has set a Prescription Drug User Fee Act action date in the fourth quarter of 2026. The application is supported by phase 3 TALAPRO-3 results showing a 52% reduction in the risk of radiographic progression or death compared with placebo plus enzalutamide.
Jeff Legos, Chief Oncology Officer, Pfizer, said:
“For men living with metastatic prostate cancer, intervening during the hormone-sensitive stage represents an important opportunity to delay progression before the disease becomes more difficult to manage.”
“If approved, TALZENNA plus XTANDI would offer patients with HRR-driven disease a new treatment option that could help them live longer without their cancer progressing. The data supporting this application also reinforce the importance of biomarker testing to inform treatment decisions as early as possible.”
Expanding Treatment Into the Hormone-Sensitive Setting
Talazoparib plus enzalutamide is currently indicated in the United States for men with HRR gene-mutated metastatic castration-resistant prostate cancer. If approved, the supplemental application would expand the use of the combination to metastatic castration-sensitive prostate cancer, an earlier stage of metastatic disease.
Metastatic castration-sensitive prostate cancer, also known as metastatic hormone-sensitive prostate cancer, is a form of advanced prostate cancer that has spread beyond the prostate but remains sensitive to androgen deprivation therapy.
According to the Pfizer announcement, approximately 5%–10% of newly diagnosed prostate cancer cases are metastatic castration-sensitive disease, and up to 30% of these patients harbor HRR gene alterations.
Read about Success Rate of Hormone Therapy for Prostate Cancer on OncoDaily.
TALAPRO-3 Trial
TALAPRO-3 is a multicenter, randomized, double-blind, placebo-controlled phase 3 trial that enrolled 599 patients with HRR gene-altered metastatic castration-sensitive prostate cancer at sites in the United States, Canada, Europe, South America, and the Asia-Pacific region.
Patients could have received no more than three months of androgen deprivation therapy, administered chemically or surgically, with or without an approved androgen receptor pathway inhibitor in the metastatic castration-sensitive setting.
Eligible participants had histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, small-cell features, or signet-cell features. Patients were also required to have an alteration in at least one HRR gene included in the trial’s 12-gene panel.
Participants were randomly assigned to receive talazoparib 0.5 mg once daily plus enzalutamide 160 mg once daily or placebo plus enzalutamide 160 mg once daily.
The primary endpoint was investigator-assessed radiographic progression-free survival, defined as the time from randomization to radiographic progression in soft tissue according to RECIST version 1.1, progression in bone according to Prostate Cancer Working Group 3 criteria, or death, whichever occurred first. Secondary endpoints included overall survival, objective response rate, duration of response, and patient-reported outcomes.
Results Presented at ASCO 2026
At the 2026 ASCO Annual Meeting, Neeraj Agarwal presented results from the phase 3 TALAPRO-3 trial. The findings were simultaneously published on May 30, 2026, in The New England Journal of Medicine.
At the February 18, 2026, data cutoff, median follow-up for radiographic progression-free survival was 37.6 months with talazoparib plus enzalutamide and 37.7 months with placebo plus enzalutamide.
Median radiographic progression-free survival was not reached with talazoparib plus enzalutamide and was 45.8 months with placebo plus enzalutamide. At three years, radiographic progression-free survival was 76.6% and 56.2%, respectively, corresponding to a 52% reduction in the risk of radiographic progression or death (HR, 0.481; 95% CI, 0.357–0.647; P<0.0001).
The benefit was observed in both biomarker subgroups. Among patients with BRCA1/2 alterations, the hazard ratio for radiographic progression or death was 0.368. Among patients without BRCA1/2 alterations, the hazard ratio was 0.567.
At the interim analysis, overall survival favored talazoparib plus enzalutamide but had not reached statistical significance. Three-year overall survival was 77.8% with talazoparib plus enzalutamide and 71.6% with placebo plus enzalutamide (HR, 0.767; 95% CI, 0.564–1.044; P=0.0905).
Grade 3–4 treatment-emergent adverse events occurred in 79% of patients receiving talazoparib plus enzalutamide and 41% of those receiving placebo plus enzalutamide. Anemia occurred in 71% of patients in the talazoparib plus enzalutamide group, including grade 3–4 anemia in 51%.
Read more about TALAPRO-3 at ASCO 2026 on OncoDaily.
How Does Talazoparib Work?
TALZENNA (talazoparib) is an oral inhibitor of poly ADP-ribose polymerase, which plays a role in DNA damage repair. Preclinical studies have shown that talazoparib blocks PARP enzyme activity and traps PARP at sites of DNA damage, leading to decreased cancer cell growth and cancer cell death.
Talazoparib was initially approved in the United States, European Union, and other regions as a single agent for adults with deleterious or suspected deleterious germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer.
How Does Enzalutamide Work?
XTANDI (enzalutamide) is an androgen receptor pathway inhibitor and a standard of care in prostate cancer.
It has received regulatory approvals in one or more countries for metastatic hormone-sensitive prostate cancer, metastatic castration-resistant prostate cancer, nonmetastatic castration-resistant prostate cancer, and nonmetastatic hormone-sensitive prostate cancer with high-risk biochemical recurrence.
Enzalutamide is approved for one or more of these indications in more than 80 countries, including the United States, European Union, and Japan. More than 1.5 million patients have been treated with enzalutamide globally.
Current Regulatory Status
Talazoparib plus enzalutamide was approved by the FDA in June 2023 for adults with HRR gene-mutated metastatic castration-resistant prostate cancer.
The combination was also approved by the European Commission in January 2024 for adults with metastatic castration-resistant prostate cancer for whom chemotherapy is not clinically indicated.
Talazoparib plus enzalutamide is currently approved for metastatic castration-resistant prostate cancer in more than 60 countries, although the specific indications vary by country.
An application for talazoparib plus enzalutamide in HRR gene-mutated metastatic castration-sensitive prostate cancer is also under review by the European Medicines Agency. The FDA has set a PDUFA action date in the fourth quarter of 2026.
The full announcement is available on Pfizer’s official website.