Pfizer announces TALZENNA, XTANDI combination data from TALAPRO-2 study

Pfizer announced results from the Phase 3 TALAPRO-2 study of TALZENNA, an oral poly ADP-ribose polymerase inhibitor, in combination with XTANDI, demonstrating a statistically significant and clinically meaningful improvement in radiographic progression-free survival compared to placebo plus XTANDI in men with metastatic castration-resistant prostate cancer, with or without homologous recombination repair gene mutations. In addition, the U.S. Food and Drug Administration has granted Priority Review for Pfizer’s supplemental new drug application for TALZENNA in combination with XTANDI for the treatment of men with mCRPC. The FDA grants Priority Review to medicines that may offer significant advances in treatment or may provide a treatment where no adequate therapy exists. The FDA’s decision on the sNDA is expected in 2023. The TALAPRO-2 results will be presented today, Thursday, February 16, at 8:00 a.m. PST during the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium as a late-breaking presentation and will be featured in the ASCO GU official press program. In the final rPFS analysis, TALZENNA plus XTANDI reduced the risk of disease progression or death by 37% versus placebo plus XTANDI. The median rPFS for the treatment arm was not reached at the time of analysis versus 21.9 months for placebo plus XTANDI. Median rPFS is reached when 50% of trial participants have had an event of disease progression or death. A trend in overall survival favoring TALZENNA plus XTANDI was also observed, though these data are immature. The final OS will be reported once the predefined number of survival events has been reached. TALAPRO-2 is the first Phase 3 study to combine TALZENNA with XTANDI in patients unselected for genetic alterations in DNA damage repair pathways, directly or indirectly involved with HRR. The study also showed clinically meaningful improvement in median rPFS for patients in the study treated with TALZENNA plus XTANDI across several prospectively assessed subgroups including HRR-deficient and HRR-non-deficient or unknown. Objective response rates, prostate-specific antigen response greater than or equal to50%, and time to PSA progression and use of subsequent cytotoxic chemotherapy and antineoplastic therapy were also significantly improved in patients treated with TALZENNA plus XTANDI versus placebo plus XTANDI. Median time to definitive clinically meaningful deterioration in global health status/quality of life was also longer in those treated with TALZENNA plus XTANDI. In the TALAPRO-2 trial, the safety of TALZENNA plus XTANDI was generally consistent with the known safety profile of each medicine. Among patients treated with TALZENNA plus XTANDI, the most common adverse events included anemia, decreased neutrophil count, fatigue, decreased platelet count, back pain and decreased white blood cell count, and decreased appetite. The most common grade greater than or equal to3 treatment emergent adverse events were anemia, low neutrophil, and low platelet counts. Among patients treated with placebo plus XTANDI, the most common AEs were fatigue, arthralgia, back pain, anemia, constipation, and decreased appetite. The most common grade greater than3 AEs were hypertension, anemia, and fatigue. TEAEs led to discontinuation of TALZENNA in 19.1% of patients versus 12.2% of placebo. Discontinuation rates of XTANDI were generally consistent across both study arms. Pfizer plans to submit detailed results from the trial for peer-reviewed publication. In addition to the FDA, Pfizer has also shared these data with the European Medicines Agency and other regulatory agencies to support regulatory filings and will provide further updates at the appropriate time.