Phase 3 TALAPRO-3 trial meets primary end point in HRR-mutated mCSPC

The phase 3 TALAPRO-3 trial (NCT04821622) has met its primary end point, demonstrating that the combination of talazoparib (Talzenna) plus enzalutamide (Xtandi) led to a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) compared with placebo plus enzalutamide in patients with HRR-mutated metastatic castration-sensitive prostate cancer (mCSPC), Pfizer announced.¹

According to Pfizer, the comparison between arms exceeded the pre-specified target hazard ratio of 0.63, and the majority of patients were free from progression at the time of analysis. The rPFS efficacy benefit was consistent across patients whose tumors harbored BRCA and non-BRCA HRR gene alterations.

Topline results also showed a strong trend toward improvement in the trial’s key secondary end point of overall survival, although the data were not mature at the time of report. Pfizer also reported that the combination showed improvements in other secondary end points such as overall response rate, duration of response, and time to prostate-specific antigen progression.

No new safety signals were observed; the safety profile for the combination was consistent with the known safety profile of the individual agents.

The combination of talazoparib plus enzalutamide was previously approved in June 2023 for adult patients with HRR-mutatated metastatic castration-resistant prostate cancer. The TALAPRO-3 trial is exploring the safety and efficacy of the combination earlier in the disease course.

“Current treatment approaches leave many patients with HRR gene-mutated metastatic castration-sensitive prostate cancer vulnerable to early disease progression,” said global lead investigator Neeraj Agarwal, MD, FASCO, professor and Presidential Endowed Chair of Cancer Research at Huntsman Cancer Institute at the University of Utah, in a news release on the results.¹ “The TALAPRO-3 results demonstrate that treatment with TALZENNA in combination with XTANDI earlier in the disease course significantly extends the time patients can live without their cancer worsening.”

In total, the phase 3, double-blind TALAPRO-3 trial enrolled 599 patients with mCSPC with alterations in at least 1 HRR gene (per HRR12 gene panel).² The study enrolled participants through clinical trial sites across the US, Canada, Europe, South America, and the Asia-Pacific region. Patients in the trial had received 3 or less months of androgen deprivation therapy (chemical or surgical) with or without an approved androgen receptor pathway inhibitor in the mCSPC setting.

Those included in the trial were randomly assigned to receive talazoparib 0.5 mg/day plus enzalutamide 160 mg/day or placebo plus enzalutamide 160 mg/day. The primary end point for the trial is rPFS, defined as the time from randomization to radiographic progression in soft tissue per RECIST v1.1 or in bone per PCWG3 criteria by investigator assessment, or death, whichever occurs first.

According to Pfizer, full results from the TALAPRO-3 trial will be shared with global health authorities for potential regulatory submissions and shared at an upcoming medical congress.

“Alterations in DNA damage repair genes, such as HRR genes, are found in approximately 25% of metastatic prostate cancers and associated with a worse prognosis and are less responsive to current standards of care, representing a group with a high unmet need,” concluded Jeff Legos, Chief Oncology Officer for Pfizer, in the news release.¹ “Talzenna plus Xtandi is already a standard of care in HRR gene-mutated metastatic castration-resistant prostate cancer, and these unprecedented results demonstrate the potential to deliver benefit earlier in the disease course. These findings underscore Pfizer’s leadership in precision medicine and commitment to bringing more personalized treatment options to people living with prostate cancer.”

REFERENCES

1. TALZENNA Plus XTANDI Significantly Improves Radiographic Progression-Free Survival in Metastatic Prostate Cancer. News release. Pfizer. March 19, 2026. Accessed March 19, 2026. https://www.pfizer.com/news/press-release/press-release-detail/talzenna-plus-xtandi-significantly-improves-radiographic

2. Study of Talazoparib With Enzalutamide in Men With DDR Gene Mutated mCSPC. ClinicalTrials.gov. Last updated March 11, 2026. Accessed March 19, 2026. https://clinicaltrials.gov/study/NCT04821622