TALENT: A Study of Talazoparib with or Without Enzalutamide in People with Prostate Cancer Who Have Previously Received Abiraterone Acetate (NCT06844383)

Currently, the use of a combination of talazoparib and enzalutamide in patients with first-line metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair (HRR) mutations who have had progression of disease during treatment with androgen-deprivation therapy (ADT) and abiraterone combination therapy has not yet been specifically studied. Very few patients in the TALAPRO-2 study had received prior abiraterone acetate with prednisone. However, the standards of care for mHSPC have changed since the study was conducted, such that currently many patients with metastatic hormone-sensitive prostate cancer (mHSPC) now receive abiraterone with prednisone with ADT. Given this, we seek to investigate two primary questions that are highly relevant to clinical practice for patients with HRR mutations:  1) Does talazoparib, as monotherapy or in combination with enzalutamide, benefit patients with mCRPC and HRR mutations after progression on abiraterone in terms disease control outcomes? and 2) Does the combination of talazoparib and enzalutamide prolong radiographic progression-free survival (rPFS) for patients with mCRPC and HRR mutations after disease progression on abiraterone versus talazoparib alone? We hypothesize that the combination of talazoparib with enzalutamide is associated with prolonged rPFS versus talazoparib alone in participants with mCRPC with HRR mutations. Secondary endpoints include prostate-specific antigen (PSA) response rates after 9 months (Cycle 10 Day 1), time to PSA progression, quality of life, and exploratory endpoints of rPFS by gene (BRCA versus non-BRCA, gene by gene and gene clusters).

TALENT will enroll patients presenting with mCRPC with prior disease progression while receiving abiraterone acetate. Talazoparib and enzalutamide (Arm A) or talazoparib alone (Arm B) will be administered along with ADT until disease progression, unacceptable toxicity, treatment delay > 60 days of talazoparib, protocol violation, withdrawal of consent, physician decision, study termination by PCCTC, lost to follow-up, or death. Talazoparib will be administered in a flat dose of 0.5 mg by mouth (PO) once daily in combination with enzalutamide at a dose of 160 mg once daily, or a flat dose of 1 mg PO once daily if administered alone.

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