Pfizer (NYSE: PFE) announced today positive results from the Phase 3 TALAPRO-2 study of TALZENNA® (talazoparib), an oral poly ADP-ribose polymerase (PARP) inhibitor, in combination with XTANDI® (enzalutamide), demonstrating a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) compared to placebo plus XTANDI in men with metastatic castration-resistant prostate cancer (mCRPC), with or without homologous recombination repair (HRR) gene mutations. In addition, the U.S. Food and Drug Administration (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 will be presented today, Thursday, February 16, at 8:00 a.m. PST 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
"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 3 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
"Patients with mCRPC need new treatment approaches that can improve outcomes, and the rPFS results from TALAPRO-2, which appears to be the longest observed in a randomized trial in this setting, demonstrate the potential of the TALZENNA and XTANDI combination, if approved, to become a new standard of care," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology and Rare Disease, Pfizer Global Product Development. "We are pleased that the FDA has granted Priority Review for our application, and we look forward to working with the Agency and global regulatory authorities to bring this treatment to men with mCRPC."
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 ≥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 >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%).
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.
Neither TALZENNA nor the combination of TALZENNA plus XTANDI has been approved by any regulatory agency for the treatment of mCRPC. 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 3 study in men with HRR-deficient metastatic castration-sensitive prostate cancer (mCSPC).
About Metastatic Castration-Resistant Prostate Cancer
Metastatic castration-resistant prostate cancer (mCRPC) is a cancer that has spread beyond the prostate gland and has progressed despite medical or surgical treatment to lower testosterone. Approximately 10%-20% of prostate cancer patients develop mCRPC within 5−7 years of diagnosis,1 and in the U.S., in 2020, approximately 60-90 thousand cases of the 3 million prostate cancer cases were mCRPC.2
About TALAPRO-2
The Phase 3 TALAPRO-2 trial is a two-part, two-cohort, multicenter, randomized, double-blind, placebo-controlled study that enrolled 1,106 patients with mCRPC (with no systemic treatments initiated after documentation of mCRPC) at sites in the U.S., Canada, Europe, South America, and the Asia-Pacific region. The study included two patient cohorts: all-comers (n=750) and those with HRR mutations (HRRm; n=380). Patients on androgen deprivation therapy (ADT) or who had bilateral orchiectomy in the trial were randomized to receive TALZENNA 0.5 mg/day plus XTANDI 160mg/day, or placebo plus XTANDI 160 mg/day.
The primary endpoint of the trial is radiographic progression-free survival (rPFS), defined as the time from the date of randomization to first objective evidence of radiographic progression by blinded independent review, or death, whichever occurs first, in both cohort 1 (all-comers) and cohort 2 (those with HRRm). The trial is still ongoing for cohort 2. Secondary endpoints include overall survival, objective response rate, duration of response, and PSA response.
