Pfizer is eyeing early use of its PARP inhibitor Tarzenna after positive results in a Phase 3 trial in metastatic hormone-sensitive prostate cancer (mHSPC).
The Phase 3 Talapro-3 trial met its primary endpoint, showing that the combination of Talzena and Pfizer and Astellas’ prostate cancer drug Extandi significantly reduced the risk of tumor progression or death compared to Extandi and placebo alone. This was targeted at patients with mHSPC mutated in the homologous recombination repair (HRR) gene, Pfizer announced in a release on Thursday, March 19th.
The company said the radiographic progression-free survival results “significantly exceeded” the pre-specified goal of a 37% improvement. Pfizer described efficacy as “consistent” between BRCA-mutant and non-BRCA-mutant subgroups.
The interim analysis also revealed what Pfizer called a “strong trend” toward improving overall survival, a key secondary endpoint. The New York drugmaker also noted benefits in other secondary endpoints, including overall response rate, duration of response, and time to PSA progression.
Following the positive results, Pfizer said it plans to discuss these results with global regulatory authorities for a potential regulatory filing.
HRR mutations are found in approximately 25% of metastatic prostate cancers and are associated with poor prognosis, Dr. Jeff Legos, Pfizer’s chief oncology officer, said in a statement. Despite existing treatments, 50% to 65% of patients with metastatic castration-sensitive prostate cancer will progress to metastatic castration-resistant prostate cancer (mCRPC) within two years, according to Pfizer.
The combination of Talzenna and Xtandi is already approved for HRR-mutant mCRPC, and Legos added that the “unprecedented results” with Tarapro 3 show the potential to benefit patients early in the disease course.
The Talapro-3 results give Pfizer a new opportunity to expand Talzenna’s indications after the FDA recently ignored the broader mCRPC population.
In May 2025, an FDA advisory committee unanimously voted against approval of Talzenna and Xtandi for patients with mCRPC without HRR mutations, based on data from the Phase 3 Tarapro 2 trial. After questioning the validity of Tarapro2’s findings in the non-mutant subgroup, the FDA followed the committee’s June recommendation in updating Talzenna’s label to include only new overall survival data in existing HRR-mutated mCRPC indications.
Tarzena faces intra-class competition in mCRPC, but could be the first PARP inhibitor to enter mHSPC. None of the other three commercially available PARP drugs have undergone phase 3 trials in mHSPC.
Compared to Xtandi, the leading androgen receptor inhibitor, Talzenna is a relatively small product within Pfizer’s oncology portfolio and PARP inhibitor class. In 2025, Talzenna generated $182 million in revenue, an increase of 55.6% over the previous year.
Xtandi received mHSPC approval from the FDA in 2019 and became the first androgen receptor inhibitor approved for non-metastatic castration-sensitive prostate cancer in 2023.
In addition to Tarzena, Pfizer is combining Xtandi with the experimental EZH2 inhibitor mebrometostat in mHSPC in the Phase 3 Mevpro-3 trial. Results from Johnson & Johnson’s Phase 3 Mevpro-1 trial of the drug and Xtandi in mCRPC following treatment with Zytiga are expected this year.
