FDA approves talazoparib with enzalutamide for HRR gene-mutated prostate cancer

The FDA approved talazoparib (Talzenna, Pfizer Inc.) in combination with enzalutamide for adults with metastatic androgen pathway modulation-naïve or -sensitive prostate cancer with homologous recombination repair (HRR) gene mutations, as detected by an FDA-authorized test. In the TALAPRO-3 trial of 599 patients, median radiographic progression-free survival was not reached with talazoparib and enzalutamide, against 45.8 months with placebo and enzalutamide (hazard ratio 0.48 [95% CI: 0.36, 0.65]; p<0.0001), the FDA said. The approval adds a use for HRR gene-mutated disease at the androgen pathway modulation-naïve or -sensitive stage, beyond the castration-resistant use on the label dated Jun 03, 2026.

Why it matters

The Talzenna label dated Jun 03, 2026 lists talazoparib as a poly (ADP-ribose) polymerase (PARP) inhibitor indicated in combination with enzalutamide for adult patients with HRR gene-mutated metastatic castration-resistant prostate cancer (mCRPC). That label version predates the October 26, 2026 approval. The FDA said it previously approved the FoundationOne CDx and FoundationOne Liquid CDx assays as companion diagnostic devices to identify patients with prostate cancer with HRR gene alterations for treatment with talazoparib in combination with enzalutamide. The FDA said full prescribing information for Talzenna will be posted on Drugs@FDA.

The TALAPRO-3 numbers

The FDA approval notice is dated October 26, 2026. The FDA reported these results from TALAPRO-3 (NCT04821622):

Median radiographic progression-free survival (rPFS), talazoparib and enzalutamide arm: not reached (NR) (95% CI: NR, NR).
Median rPFS, placebo and enzalutamide arm: 45.8 months (95% CI: 37.7, NR).
Hazard ratio: 0.48 (95% CI: 0.36, 0.65); p<0.0001.

The FDA said there was "a statistically significant improvement in rPFS for the talazoparib and enzalutamide arm." The FDA also said overall survival (OS) was an additional efficacy outcome measure and that OS data were immature at the time of the rPFS analysis.

Trial design and participants

The FDA said TALAPRO-3 was a randomized, double-blind, placebo-controlled trial. It randomized 599 patients with HRR gene-mutated mAPMN/S prostate cancer 1:1 to enzalutamide plus either talazoparib or placebo, given daily. All patients also received continuous androgen deprivation therapy.

Mutation status of the HRR genes ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2 or RAD51C was determined prospectively, using tumor tissue or circulating tumor DNA (ctDNA)-based next generation sequencing tests, the FDA said.

The major efficacy outcome measure was rPFS according to RECIST, version 1.1 and PCWG3 (bone) criteria, assessed by investigator. The TALAPRO-3 study record lists Pfizer as the lead sponsor and Astellas Pharma Inc as a collaborator. It defines the primary outcome as the "time from the date of randomization to first objective evidence of radiographic progression or death, whichever occurs first."

Dosage and safety

The FDA said the recommended talazoparib dose is 0.5 mg orally once daily with enzalutamide until disease progression or unacceptable toxicity. Patients receiving talazoparib and enzalutamide should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had a bilateral orchiectomy, the FDA said.

The prescribing information includes warnings and precautions for myelodysplastic syndrome/acute myeloid leukemia, myelosuppression, and embryo-fetal toxicity, the FDA said. The FDA page lists no adverse event rates.

Review pathway

The FDA said the application was granted priority review. The review was conducted under Project Orbis, with the FDA collaborating with the Australian Therapeutic Goods Administration (TGA) and Health Canada. The FDA said the application reviews are ongoing at the other regulatory agencies. The review also used the Assessment Aid, a voluntary submission from the applicant to help the FDA's assessment.