辉瑞TALZENNA联合XTANDI获FDA优先审评用于HRR突变转移性去势敏感前列腺癌

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 profile consistent 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 .
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 www.clinicaltrials.gov .
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 fo