Pfizer’s TALZENNA Combo Hits rPFS Goal in TALAPRO-3

Pfizer Inc. announced positive topline results from the Phase 3 TALAPRO-3 study (NCT04821622) evaluating TALZENNA® (talazoparib) in combination with XTANDI® (enzalutamide) in patients with homologous recombination repair (HRR) gene-mutated metastatic castration-sensitive prostate cancer (mCSPC), also known as metastatic hormone-sensitive prostate cancer.

The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) with TALZENNA plus XTANDI compared with placebo plus XTANDI. The treatment effect exceeded the pre-specified hazard ratio target of 0.63, with most patients remaining progression-free at the time of analysis. Benefit was observed across tumors with BRCA and non-BRCA HRR mutations.

At the interim analysis, the combination also showed a strong trend toward improved overall survival, a key secondary endpoint. Improvements were also reported in overall response rate, duration of response, and time to prostate-specific antigen (PSA) progression. The safety profile was consistent with the known safety of each medicine, with no new safety signals identified.

According to the study’s global lead investigator Neeraj Agarwal, M.D., introducing TALZENNA earlier in the disease course may help delay disease progression in patients with HRR-mutated metastatic prostate cancer.

Pfizer noted that HRR gene alterations occur in roughly 25% of metastatic prostate cancers and are associated with poorer outcomes. The company said the results support the potential role of the combination earlier in the treatment pathway.

The TALZENNA plus XTANDI regimen is currently investigational for HRR-mutated mCSPC, and the company plans to present detailed results at an upcoming medical congress and discuss potential regulatory submissions with health authorities.

The TALAPRO-3 trial (NCT04821622) enrolled 599 patients with HRR gene-mutated metastatic castration-sensitive prostate cancer across multiple global sites. Participants were randomized to receive TALZENNA 0.5 mg once daily plus XTANDI 160 mg daily or placebo plus XTANDI. The primary endpoint was investigator-assessed rPFS, with secondary endpoints including overall survival, objective response rate, PSA response, and patient-reported outcomes.

Jeff Legos, Chief Oncology Officer, Pfizer said HRR gene alterations occur in about 25% of metastatic prostate cancers and are associated with poorer outcomes, and the positive TALAPRO-3 results suggest TALZENNA plus XTANDI could benefit patients earlier in the disease course.

TALZENNA is an oral PARP inhibitor that blocks DNA damage repair in cancer cells. The drug is already approved in combination with XTANDI in HRR gene-mutated metastatic castration-resistant prostate cancer (mCRPC) and is authorized in more than 60 countries, including the United States and the European Union.

For full prescribing details, including safety information, warnings, precautions, adverse reactions, and drug interactions, see the U.S. Prescribing Information:
https://labeling.pfizer.com/showlabeling.aspx?id=13555

References

TALZENNA Plus XTANDI Significantly Improves Radiographic Progression-Free Survival in Metastatic Prostate Cancer, 19 March 2026, TALZENNA Plus XTANDI Significantly Improves Radiographic Progression-Free Survival in Metastatic Prostate Cancer | Pfizer

Study of Talazoparib with Enzalutamide in Men with DDR Gene Mutated mCSPC, ClinicalTrials.gov ID NCT04821622, https://clinicaltrials.gov/study/NCT04821622