Talazoparib/Enzalutamide Combo Meets rPFS End Point in Untreated Metastatic CRPC

The addition of talazoparib (Talzenna) to enzalutamide (Xtandi) produced a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) vs enzalutamide plus placebo in previously untreated patients with metastatic castration-resistant prostate cancer (mCRPC), with or without homologous recombination repair (HRR) gene mutations, meeting the primary end point of the phase 3 TALAPRO-2 trial (NCT03395197).

Results for the primary end point exceeded the prespecified hazard ratio of 0.696. Detailed findings from the trial will be presented at a medical congress in the near future, and data will be submitted to global regulatory authorities to potentially support a regulatory filing.

“[Enzalutamide] is a global standard of care, with overall survival [OS] demonstrated in mCRPC, nonmetastatic CRPC, and metastatic castration-sensitive prostate cancer [mCSPC],” Chris Boshoff, MD, PhD, chief development officer of Oncology and Rare Disease at Pfizer Global Product Development, stated in a press release. “We are very pleased with the strong findings from TALAPRO-2, and although no definitive conclusions can be made across trials, the rPFS appears to be the longest observed in a randomized trial in this setting.

“These data highlight the potential for [talazoparib] in combination with [enzalutamide], if approved, to become a new standard of care for mCRPC, irrespective of HRR gene mutation status. We look forward to discussing these data with global health authorities.”

The two-part, two-cohort, multicenter, randomized, double-blind, placebo-controlled TALAPRO-2 trial enrolled 1,095 patients with mCRPC who received no systemic treatments after documentation of mCRPC. The two cohorts consisted of all-comers (cohort 1; n = 750) and those with HRR mutations (cohort 2; n = 380).

Patients on androgen deprivation therapy (ADT) or who had bilateral orchiectomy in the trial were randomly assigned to receive 0.5 mg of talazoparib per day plus 160 mg of enzalutamide per day, or placebo plus 160 mg of enzalutamide per day.

The primary end point was rPFS for cohort 1 and cohort 2. Notably, the trial is ongoing for cohort 2. Secondary end points included investigator-assessed rPFS, OS, overall response rate (ORR), duration of response (DOR), prostate-specific antigen (PSA) response, time to PSA progression, and safety.

Additional data showed a trend toward an OS benefit for the combination vs enzalutamide alone, though those data are not mature. Benefits were also observed in other secondary end points, including investigator assessed rPFS, PSA response, time to PSA progression, and ORR.

Regarding toxicity, the safety profile of talazoparib plus enzalutamide was generally consistent with the known safety of each agent.

“These exciting results from TALAPRO-2 underscore our long-standing commitment to men living with prostate cancer and delivering the next scientific breakthroughs,” Suneet Varma, president, Global Oncology, Pfizer, stated in a press release. “Based on these compelling combination data with [enzalutamide], we believe [talazoparib] in prostate cancer may become the next potential blockbuster opportunity in our leading Pfizer Oncology portfolio, subject to regulatory approval.”

The combination of talazoparib and enzalutamide is also being evaluated vs enzalutamide alone in the phase 3 TALAPRO-3 trial (NCT04821622) in patients with HRR-deficient mCSPC.

Reference

Pfizer announces positive topline results from phase 3 TALAPRO-2 trial. News release. Pfizer. October 4, 2022. Accessed October 4, 2022. https://bit.ly/3EbhRPj