Talazoparib Tosylate

Supplemental application aims to expand use to men with HRR gene-mutated metastatic castration-sensitive prostate cancer Filing supported by Phase 3 TALAPRO-3 data demonstrating greater than 50% improvement in radiographic progression-free survival, with consistent benefit across BRCA and non-BRCA HRR gene alterations NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) today announced that the U.S. Food and Drug Administration (FDA) accepted for Priority Review a supplemental New Drug Application (sNDA) for TALZENNA ® (talazoparib), an oral poly ADP-ribose polymerase (PARP) inhibitor, in combination with XTANDI ® (enzalutamide), an androgen receptor pathway inhibitor (ARPI), in men with homologous recombination repair (HRR) gene-altered metastatic castration-sensitive prostate cancer (mCSPC), also known as metastatic hormone-sensitive prostate cancer (mHSPC). The FDA has set a Prescription Drug User Fee Act (PDUFA) action date in the last quarter of 2026. TALZENNA plus XTANDI is currently indicated in the U.S. for men with HRR gene-mutated metastatic castration-resistant prostate cancer (mCRPC). If approved, the sNDA would expand the combination's use to mCSPC, an earlier stage of disease. “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,” said Jeff Legos, Chief Oncology Officer, Pfizer. “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.” The application is supported by data from the Phase 3 TALAPRO-3 trial ( NCT04821622 ) which showed TALZENNA plus XTANDI reduced the risk of radiographic progression or death by 52% versus placebo plus XTANDI, with consistent benefit across patients with BRCA and non- BRCA HRR gene alterations, and a safety pro with the known profiles of each agent and no new safety signals. These results were presented at the 2026 American Society of Clinical Oncology Annual Meeting and simultaneously published in The New England Journal of Medicine . ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); The use of TALZENNA plus XTANDI in HRR gene-mutated mCSPC is also under review by the European Medicines Agency. TALZENNA plus XTANDI is currently approved for mCRPC in more than 60 countries, with specific indications varying by country. About mCSPC Metastatic castration-sensitive prostate cancer (mCSPC) is a form of advanced prostate cancer – the second most common cancer in men worldwide – that has spread beyond the prostate but is still sensitive to androgen deprivation therapy. 1,2 Approximately 5-10% of newly diagnosed cases are mCSPC, 3,4 and up to 30% of these patients harbor HRR gene alterations. 5 About TALAPRO-3 The Phase 3 TALAPRO-3 trial is a multicenter, randomized, double-blind, placebo-controlled study that enrolled 599 patients with mCSPC (with ≤3 months of ADT [chemical or surgical] with or without an approved ARPI in the mCSPC setting) at sites in the U.S., Canada, Europe, South America, and the Asia-Pacific region. Patients with histologically/cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, small cell, or signet cell features and with alterations in one or more HRR genes (as per HRR12 gene panel) in the trial were randomized to receive TALZENNA 0.5 mg/day plus XTANDI 160mg/day, or placebo plus XTANDI 160mg/day. The primary endpoint of the trial is investigator-assessed rPFS, defined as the time from the date of randomization to radiographic progression in soft tissue per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or in bone per Prostate Cancer Working Group 3 (PCWG3) criteria by investigator assessment, or death, whichever occurs first. Secondary endpoints include OS, objective response rate, duration of response, and patient-reported outcomes. For more information on the TALAPRO-3 trial ( NCT04821622 ), go to . About TALZENNA ® (talazoparib) TALZENNA is an oral inhibitor of poly ADP-ribose polymerase (PARP), which plays a role in DNA damage repair. Preclinical studies have demonstrated that TALZENNA blocks PARP enzyme activity and traps PARP at the site of DNA damage, leading to decreased cancer cell growth and cancer cell death. TALZENNA was initially approved in the U.S., EU, and multiple other regions as a single agent for the treatment of adult patients with deleterious or suspected deleterious gBRCAm HER2-negative locally advanced or metastatic breast cancer. TALZENNA in combination with XTANDI was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with HRR gene-mutated mCRPC in June 2023. The combination was also approved by the European Commission in January 2024 for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated. TALZENNA in combination with XTANDI is approved in more than 60 countries, indications vary by country. TALZENNA ® (talazoparib) Indication in the U.S. TALZENNA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for: HRR gene-mutated mCRPC: In combination with enzalutamide for the treatment of adult patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC). Breast Cancer: As a single agent, for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer. Select patients for therapy based on an FDA-approved companion diagnostic for TALZENNA. TALZENNA ® (talazoparib) Important Safety Information WARNINGS and PRECAUTIONS Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) , including cases with a fatal outcome, has been reported in patients who received TALZENNA. Overall, MDS/AML has been reported in 0.4% (3 out of 788) of solid tumor patients treated with TALZENNA as a single agent in clinical studies. In TALAPRO-2, MDS/AML occurred in 2 out of 511 (0.4%) patients treated with TALZENNA and enzalutamide and in 0 out of 517 (0%) patients treated with placebo and enzalutamide. The durations of TALZENNA treatment in these 5 patients prior to developing MDS/AML were 0.3, 1, 2, 3, and 5 years. Most of these patients had received previous chemotherapy with platinum agents and/or other DNA damaging agents including radiotherapy. Do not start TALZENNA until patients have adequately recovered from hematological toxicity caused by previous chemotherapy. Monitor blood counts monthly during treatment with TALZENNA. For prolonged hematological toxicities, interrupt TALZENNA and monitor blood counts weekly until recovery. If counts do not recover within 4 weeks, refer the patient to a hematologist for further investigations including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue TALZENNA. Myelosuppression consisting of anemia, neutropenia, and/or thrombocytopenia, have been reported in patients treated with TALZENNA. In TALAPRO-2, Grade ≥3 anemia, neutropenia, and thrombocytopenia were reported, respectively, in 48%, 19%, and 9% of patients receiving TALZENNA and enzalutamide. Forty-two percent of patients (216/511) required a red blood cell transfusion, including 25% (127/511) who required more than one transfusion. Discontinuation due to anemia, neutropenia, and thrombocytopenia occurred, respectively, in 8%, 3%, and 0.4% of patients. Withhold TALZENNA until patients have adequately recovered from hematological toxicity caused by previous therapy. Monitor blood counts monthly during treatment with TALZENNA. If hematological toxicities do not resolve within 28 days, discontinue TALZENNA and refer the patient to a hematologist for further investigations including bone marrow analysis and blood sample for cytogenetics. Embryo-Fetal Toxicity TALZENNA can cause fetal harm when administered to pregnant women. Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 4 months following the last dose of TALZENNA. ADVERSE REACTIONS Serious adverse reactions reported in >2% of patients included anemia (9%) and fracture (3%). Fatal adverse reactions occurred in 1.5% of patients, including pneumonia, COVID infection, and sepsis (1 patient each). The most common adverse reactions (≥ 10%, all Grades), including laboratory abnormalities, for patients in the TALAPRO-2 study who received TALZENNA with enzalutamide vs patients receiving placebo with enzalutamide were hemoglobin decreased (79% vs 34%), neutrophils decreased (60% vs 18%), lymphocytes decreased (58% vs 36%), fatigue (49% vs 40%), platelets decreased (45% vs 8%), calcium decreased (25% vs 11%), nausea (21% vs 17%), decreased appetite (20% vs 14%), sodium decreased (22% vs 20%), phosphate decreased (17% vs 13%), fractures (14% vs 10%), magnesium decreased (14% vs 12%), dizziness (13% vs 9%), bilirubin increased (11% vs 7%), potassium decreased (11% vs 7%), and dysgeusia (10% vs 4.5%). Clinically relevant adverse reactions in 2%) in the XTANDI arm compared to placebo in the pooled, randomized, placebo-controlled studies are hemoglobin decrease, neutrophil count decreased, white blood cell decreased, hyperglycemia, hypermagnesemia, hyponatremia, hypophosphatemia, and hypercalcemia. Hypertension: In the combined data from five randomized placebo-controlled clinical trials, hypertension was reported in 14.2% of XTANDI patients and 7.4% of placebo patients. Hypertension led to study discontinuation in < 1% of patients in each arm. Drug Interactions Effect of Other Drugs on XTANDI Avoid coadministration with strong CYP2C8 inhibitors. If coadministration cannot be avoided, reduce the dosage of XTANDI. Avoid coadministration with strong CYP3A4 inducers. If coadministration cannot be avoided, increase the dosage of XTANDI. Effect of XTANDI on Other Drugs Avoid coadministration with certain CYP3A4, CYP2C9, and CYP2C19 substrates for which minimal decrease in concentration may lead to therapeutic failure of the substrate. If coadministration cannot be avoided, increase the dosage of these substrates in accordance with their Prescribing Information. In cases where active metabolites are formed, there may be increased exposure to the active metabolites. Please access this link for XTANDI’S US Full Prescribing Information for additional safety information. About Pfizer Oncology At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and multispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, gastrointestinal cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives. About Pfizer: Breakthroughs That Change Patients’ Lives At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at . In addition, to learn more, please visit us on and follow us on X at @Pfizer and @Pfizer News , LinkedIn , YouTube and like us on Facebook at Facebook.com/Pfizer . About the Pfizer/Astellas Collaboration In October 2009, Medivation, Inc., which is now part of Pfizer (NYSE: PFE), and Astellas (TSE: 4503) entered into a global agreement to jointly develop and commercialize XTANDI ® (enzalutamide). The companies jointly commercialize XTANDI in the United States, and Astellas has responsibility for manufacturing and all additional regulatory filings globally, as well as commercializing XTANDI outside the United States. Disclosure Notice The information contained in this release is as of July 22, 2026. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. This release contains forward-looking information about Pfizer Oncology, TALZENNA and XTANDI, including their potential benefits, the TALAPRO-3 results, and a supplemental New Drug Application (sNDA) for TALZENNA in combination with XTANDI to potentially expand the use of TALZENNA plus XTANDI to men with HRR gene-mutated metastatic castration-sensitive prostate cancer, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, uncertainties regarding the commercial success of TALZENNA in combination with XTANDI; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; whether the TALAPRO-3 trial will meet the key secondary endpoint for overall survival; risks associated with initial, preliminary or interim data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when applications for TALZENNA, XTANDI or a combination may be filed in any jurisdictions for any potential indications; whether and when any such applications for TALZENNA, XTANDI or a combination that may be pending or filed may be approved by regulatory authorities (including the supplemental New Drug Application filed with the FDA for TALZENNA in combination with XTANDI for men with HRR gene-mutated mCSPC and the application filed with the EMA for TALZENNA in combination with XTANDI for men with HRR gene-mutated mCSPC), which will depend on myriad factors, including making a determination as to whether the product’s benefits outweigh its known risks and determination of the product’s efficacy and, if approved, whether TALZENNA, XTANDI or a combination will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of TALZENNA, XTANDI or a combination; risks and uncertainties related to issued or future executive orders or other new, or changes in, laws or regulations; uncertainties regarding the impact of COVID-19 on Pfizer’s business, operations and financial results; and competitive developments. 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A supplemental New Drug Application (sNDA) for Pfizer’s Talzenna (talazoparib) in combination with Xtandi (enzalutamide) has been accepted for Priority Review by the US FDA. The application is to treat men with homologous recombination repair (HRR) gene-altered metastatic castration-sensitive prostate cancer (mCSPC), also known as metastatic hormone-sensitive prostate cancer (mHSPC). Talzenna (talazoparib) is an oral poly ADP-ribose polymerase (PARP) inhibitor and Xtandi (enzalutamide) is an androgen receptor pathway inhibitor (ARPI). The combination is currently indicated in the US for men with HRR gene-mutated metastatic castration-resistant prostate cancer (mCRPC). If approved, the sNDA would expand the combination’s use to mCSPC, an earlier stage of disease. Metastatic castration-sensitive prostate cancer (mCSPC) is a form of advanced prostate cancer – the second most common cancer in men worldwide – that has spread beyond the prostate but is still sensitive to androgen deprivation therapy. Approximately 5-10% of newly diagnosed cases are mCSPC, and up to 30% of these patients harbour HRR gene alterations. “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,” said Jeff Legos, Chief Oncology Officer, Pfizer. “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 reinforces the importance of biomarker testing to inform treatment decisions as early as possible.” The application is supported by data from the phase 3 TALAPRO-3 trial (NCT04821622) which showed Talzenna plus Xtandi reduced the risk of radiographic progression or death by 52% versus placebo plus Xtandi, with consistent benefit across patients with BRCA and non-BRCA HRR gene alterations. The safety profile was consistent with the known profiles of each agent and there were no new safety signals. The results were presented at the 2026 American Society of Clinical Oncology Annual Meeting and simultaneously published in The New England Journal of Medicine . The use of Talzenna plus Xtandi in HRR gene-mutated mCSPC is also under review by the European Medicines Agency. Talzenna plus Xtandi is currently approved for mCRPC in more than 60 countries, with specific indications varying by country. The FDA has set a Prescription Drug User Fee Act (PDUFA) action date in the last quarter of 2026.