Positive Talzenna + Xtandi combination data from phase III TALAPRO-2 Study in men with metastatic castration-resistant prostate cancer

In addition, the FDA) has granted Priority Review for Pfizer’s supplemental new drug application (sNDA) for Talzenna in combination with Xtandi for the treatment of men with mCRPC. The FDA grants Priority Review to medicines that may offer significant advances in treatment or may provide a treatment where no adequate therapy exists. The FDA’s decision on the sNDA is expected in 2023.

The TALAPRO-2 results were presented during the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) as a late-breaking presentation (Abstract LBA17) and will be featured in the ASCO GU official press program.

In the final rPFS analysis, Talzenna plus Xtandi reduced the risk of disease progression or death by 37% versus placebo plus Xtandi (Hazard Ratio [HR]: 0.63; 95% Confidence Interval [CI], 0.51–0.78; P< 0.001). The median rPFS for the treatment arm was not reached at the time of analysis versus 21.9 months for placebo plus Xtandi. Median rPFS is reached when 50% of trial participants have had an event of disease progression or death.

"Novel hormone therapies dramatically changed outcomes for patients with mCRPC in the last decade, and the results from the TALAPRO-2 study show that the addition of talazoparib to the existing standard of care adds significant clinical benefit,” said Neeraj Agarwal, M.D., FASCO, Professor of Oncology and Presidential Endowed Chair of Cancer Research at Huntsman Cancer Institute, University of Utah, and lead investigator for TALAPRO-2. “In addition to delaying disease progression, this combination delayed prostate-specific antigen progression and time to chemotherapy without adversely impacting patient quality of life. The TALAPRO-2 results support the potential for this combination to be practice-changing, with strong, highly consistent efficacy and observations in mCRPC patients both with or without HRR gene mutations, and across clinically relevant sub-populations.”

A trend in overall survival (OS) favoring Talzenna plus Xtandi was also observed, though these data are immature. The final OS will be reported once the predefined number of survival events has been reached. TALAPRO-2 is the first Phase III study to combine Talzenna with Xtandi in patients unselected for genetic alterations in DNA damage repair pathways, directly or indirectly involved with HRR.

The study also showed clinically meaningful improvement in median rPFS for patients in the study treated with Talzenna plus Xtandi across several prospectively assessed subgroups including HRR-deficient (HR, 0.46; 95% CI, 0.30–0.70; P<0.001) and hrr-non-deficient or unknown (hr, 0.70; 95% ci, 0.54–0.89; p="0.004)." objective response rates, prostate-specific antigen (psa) response ?50%, and time to psa progression and use of subsequent cytotoxic chemotherapy and antineoplastic therapy were also significantly improved in patients treated with talzenna plus xtandi versus placebo plus xtandi. median time to definitive clinically meaningful deterioration in global health status quality of life was also longer in those treated with talzenna plus xtandi (30.8 vs 25.0 months, respectively; hr, 0.78; 95% ci, 0.62–0.99; p="0.04)."

In the TALAPRO-2 trial, the safety of Talzenna plus Xtandi was generally consistent with the known safety profile of each medicine. Among patients treated with Talzenna plus Xtandi, the most common adverse events (AE) (greater than 20% of participants, all grades) included anemia (65.8%), decreased neutrophil count (35.7%), fatigue (33.7), decreased platelet count (24.6%), back pain and decreased white blood cell count (22.1% each), and decreased appetite (21.6%). The most common grade ,greater than 3 treatment emergent adverse events (TEAEs) were anemia (46.5%), low neutrophil (18.3%), and low platelet counts (7.3%). Among patients treated with placebo plus Xtandi, the most common AEs (greater than 15%) were fatigue (29.4%), arthralgia (19.7%), back pain (18.0%), anemia (17.5%), constipation (17.0%), and decreased appetite (15.7%). The most common grade,greater than 3 AEs, were hypertension (7.5%), anemia (4.2%), and fatigue (2.0%). TEAEs led to discontinuation of Talzenna in 19.1% of patients versus 12.2% of placebo. Discontinuation rates of Xtandi were generally consistent across both study arms (10.8% vs 11.0%).

In addition to the TALAPRO-2 trial, the combination of Talzenna plus Xtandi is being investigated in the TALAPRO-3 trial (NCT04821622), a global, randomized, double-blind, placebo-controlled Phase III study in men with HRR-deficient metastatic castration-sensitive prostate cancer (mCSPC).

Pfizer plans to submit detailed results from the trial for peer-reviewed publication. In addition to the FDA, Pfizer has also shared these data with the European Medicines Agency and other regulatory agencies to support regulatory filings and will provide further updates at the appropriate time.