Pfizer has announced positive topline results from the phase-III TALAPRO-3 study of TALZENNA (talazoparib), an oral Poly ADP-Ribose Polymerase (PARP) inhibitor, in combination with XTANDI (enzalutamide), an Androgen Receptor Pathway Inhibitor (ARPI), in people with Homologous Recombination Repair (HRR) gene-mutated metastatic Castration-Sensitive Prostate Cancer (mCSPC), also known as metastatic Hormone-Sensitive Prostate Cancer (mHSPC).

The study met its primary endpoint, with TALZENNA plus XTANDI demonstrating an improvement in radiographic Progression-Free Survival (rPFS), compared to placebo plus XTANDI. The results markedly exceeded the pre-specified target hazard ratio of 0.63, with the majority of patients remaining progression-free at the time of analysis. Consistent efficacy benefit was also observed in patients whose tumours harboured BRCA and non-BRCA HRR gene alterations.

“Current treatment approaches leave many patients with HRR gene-mutated metastatic castration-sensitive prostate cancer vulnerable to early disease progression. The TALAPRO-3 results demonstrate that treatment with TALZENNA, in combination with XTANDI, earlier in the disease course significantly extends the time patients can live without their cancer worsening,” said Neeraj Agarwal, MD, FASCO, Professor and Presidential Endowed Chair – Cancer Research, Huntsman Cancer Institute, University of Utah, and global lead investigator for TALAPRO-3.

At the time of the interim analysis, results showed a strong trend towards improved Overall Survival (OS), a key secondary endpoint. Benefits were also observed in other secondary endpoints, including Overall Response Rate, duration of response and time to Prostate-Specific Antigen (PSA) progression. The safety of TALZENNA plus XTANDI was consistent with the known safety profile of each medicine, and no new safety signals were identified.

“Alterations in DNA damage repair genes, such as HRR genes, are found in approximately 25 percent of metastatic prostate cancers and associated with a worse prognosis, and are less responsive to current standards of care, representing a group with a high unmet need. TALZENNA plus XTANDI is already a standard of care in HRR gene-mutated metastatic castration-resistant prostate cancer, and these unprecedented results demonstrate the potential to deliver benefit earlier in the disease course. These findings underscore Pfizer’s leadership in precision medicine and commitment to bringing more personalised treatment options to people living with prostate cancer,” said Jeff Legos, Chief Oncology Officer, Pfizer.

TALZENNA plus XTANDI in HRR gene-mutated mCSPC is an investigational treatment regimen. The TALAPRO-3 results will be submitted for presentation at an upcoming medical congress, and will be discussed with global health authorities for potential regulatory submissions.

TALZENNA plus XTANDI is currently approved in 60 countries, including in the United States (US) for adults with HRR gene-mutated mCRPC and in the European Union (EU) for adults with mCRPC in whom chemotherapy is not clinically indicated.

The phase-III TALAPRO-3 trial is a multicentre, randomised, 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 US, 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 randomised 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 radiographic progression-free survival (rPFS), defined as the time from the date of randomisation to radiographic progression in soft tissue per Response Evaluation Criteria in Solid Tumours 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 overall survival (OS), Objective Response Rate (ORR), Duration of Response (DOR), Prostate-Specific Antigen (PSA) response and patient-reported outcomes.