FDA approves talazoparib with enzalutamide for metastatic androgen pathway modulation-naïve or -sensitive prostate cancer with HRR gene mutations

On October 26, 2026, the US Food and Drug Administration (FDA) approved talazoparib (Talzenna, Pfizer Inc.) in combination with enzalutamide for the treatment of adults with metastatic androgen pathway modulation-naïve or -sensitive (mAPMN/S) prostate cancer with homologous recombination repair (HRR) gene mutations, as detected by an FDA-authorized test.

The FDA previously approved 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.

Efficacy and Safety

Efficacy was evaluated in TALAPRO-3 (NCT04821622), a randomized, double-blind, placebo-controlled trial in which 599 patients with HRR gene-mutated mAPMN/S prostate cancer were randomized 1:1 to receive enzalutamide plus either talazoparib or placebo daily. All patients also received continuous androgen deprivation therapy. Mutation status of 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 major efficacy outcome measure was radiographic progression-free survival (rPFS) according to RECIST, version 1.1 and PCWG3 (bone) criteria, assessed by investigator. An additional efficacy outcome measure was overall survival (OS). There was a statistically significant improvement in rPFS for the talazoparib and enzalutamide arm, with median rPFS not reached (NR) (95% CI: NR, NR) in the talazoparib and enzalutamide arm and 45.8 months (95% CI: 37.7, NR) in the placebo and enzalutamide arm (Hazard Ratio 0.48 [95% CI: 0.36, 0.65]; p<0.0001). At the time of the rPFS analysis, OS data were immature.

The prescribing information includes warnings and precautions for myelodysplastic syndrome/acute myeloid leukemia, myelosuppression, and embryo-fetal toxicity.

Recommended Dosage

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

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA) and Health Canada. The application reviews are ongoing at the other regulatory agencies.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

Source: FDA