The FDA accepted Pfizer’s sNDA for TALZENNA plus XTANDI under Priority Review for HRR gene-altered mCSPC, supported by positive Phase 3 TALAPRO-3 results.
Written By: Kirti Kumbhar, M. Pharm (QA)
Reviewed By: Pharmacally Editorial Team
Pfizer’s supplemental New Drug Application for TALZENNA (talazoparib) plus XTANDI (enzalutamide) has been accepted for Priority Review by the U.S. Food and Drug Administration for adults with homologous recombination repair (HRR) gene-altered metastatic castration-sensitive prostate cancer (mCSPC). The application is supported by Phase 3 TALAPRO-3 data showing the combination significantly delayed disease progression compared with XTANDI alone, potentially expanding targeted treatment options earlier in the disease course. The findings were presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in The New England Journal of Medicine.
Metastatic castration-sensitive prostate cancer is an advanced form of prostate cancer that has spread beyond the prostate but remains responsive to androgen deprivation therapy (ADT). Approximately 5% to 10% of newly diagnosed prostate cancer cases are mCSPC, and up to 30% of these patients harbor HRR gene alterations. These genetic alterations impair DNA repair mechanisms, making tumors potentially susceptible to treatment with PARP inhibitors such as talazoparib.
Targeting DNA Repair Defects Earlier in Advanced Prostate Cancer
TALZENNA is an oral poly (ADP-ribose) polymerase (PARP) inhibitor that exploits defects in DNA damage repair pathways, particularly in tumors carrying HRR gene alterations such as BRCA1, BRCA2, ATM, and other related genes. XTANDI is an androgen receptor pathway inhibitor that suppresses androgen signaling, a key driver of prostate cancer growth.
Combining androgen receptor inhibition with PARP inhibition may enhance antitumor activity by increasing DNA damage in HRR-deficient tumors and delaying disease progression. This biomarker-guided approach has emerged as an important strategy for personalizing treatment in advanced prostate cancer.
TALAPRO-3 Trial Showed Significant Delay in Disease Progression
The regulatory submission is based on results from the global Phase 3 TALAPRO-3 trial (NCT04821622), which evaluated TALZENNA plus XTANDI versus placebo plus XTANDI in patients with HRR gene-altered mCSPC.
The study met its primary endpoint, demonstrating a statistically significant improvement in radiographic progression-free survival (rPFS). The combination reduced the risk of radiographic progression or death by 52% compared with XTANDI alone. Clinical benefit was observed across key HRR subgroups, while the safety profile remained consistent with the known safety profiles of both medicines, with no new safety signals identified.
The results support introducing PARP inhibition during the hormone-sensitive stage, when delaying progression may extend disease control before the development of castration-resistant prostate cancer.
Biomarker Testing Remains Central to Patient Selection
Jeff Legos, Chief Oncology Officer at Pfizer, said treating metastatic prostate cancer during its hormone-sensitive stage provides an important opportunity to delay progression before the disease becomes more difficult to manage.
He added that the TALAPRO-3 findings support a potential new treatment option for patients with HRR-driven disease while reinforcing the importance of biomarker testing to identify eligible patients as early as possible and guide treatment decisions.
XTANDI is an established androgen receptor pathway inhibitor approved for multiple prostate cancer indications, including metastatic hormone-sensitive, metastatic castration-resistant, non-metastatic castration-resistant, and high-risk non-metastatic hormone-sensitive prostate cancer with biochemical recurrence. The therapy is approved in more than 80 countries, including the United States, European Union, and Japan, and has been used to treat more than 1.5 million patients worldwide.
Regulatory Path Forward
The FDA has granted Priority Review to Pfizer’s supplemental New Drug Application for TALZENNA plus XTANDI in adults with HRR gene-altered metastatic castration-sensitive prostate cancer. The application is supported by positive Phase 3 TALAPRO-3 data and reflects continued efforts to move biomarker-guided therapies earlier in the treatment of advanced prostate cancer. Under the Priority Review designation, the FDA is expected to complete its review within an expedited timeline.
Reference
About the Writer
Kirti Kumbhar (LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.