Pfizer Announces Positive Phase 2 Data for Talazoparib in Advanced Prostate Cancer

Compiled and Translated by | Fan Dongdong

The latest Phase II TALAPRO-1 clinical trial of Pfizer's BRCA-targeted drug talazoparib demonstrates that treatment with the drug can slow tumor growth in patients with advanced prostate cancer.

According to data published in *The Lancet Oncology*, the TALAPRO-1 trial was led by Professor Johann de Bono of The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust. Over the 29-month trial period, patients from hospitals, cancer centers, and medical centers across 14 different countries participated in this open-label phase II clinical trial. The results showed that at a median follow-up of 16.4 months, the objective response rate (per RECIST 1.1) among 104 evaluable patients was 29.8% (n = 31), with BRCA1/2 being the most common genetic alteration in this patient cohort.

Among evaluable patients assessed at baseline and post-baseline, 80% experienced a reduction in tumor burden, 72% showed decreased PSA levels, and 82% had reduced circulating tumor cell counts. Regarding safety, the most frequently reported grade 3/4 treatment-emergent adverse events (TEAEs) were anemia (31%), thrombocytopenia (9%), and neutropenia (8%). Serious treatment-emergent adverse events occurred in 34% of patients. No treatment-related deaths were reported.

This drug is a PARP inhibitor developed by Pfizer, a therapeutic class that has emerged as a prominent target in oncology in recent years. Leveraging the principle of synthetic lethality, PARP inhibitors function as DNA repair inhibitors and/or cell cycle checkpoint inhibitors. Following administration, both single-strand and double-strand DNA damage repair pathways are simultaneously inhibited. Consequently, tumor cells lose their DNA repair capacity, leading to defective repair and subsequent cell death. This therapy provides a novel potential treatment option for male patients with advanced prostate cancer who have previously been treated with chemotherapy and/or enzalutamide and/or abiraterone.

The drug was first approved by the U.S. Food and Drug Administration (FDA) in 2018 for the treatment of patients with deleterious or suspected deleterious germline BRCA mutations (gBRCAm), HER2-negative locally advanced or metastatic breast cancer (MBC). Other previously approved PARP inhibitors include olaparib, rucaparib, niraparib, and talazoparib.

The trial confirmed that approximately half of the patients with BRCA2 or BRCA1 defects achieved a clinical response to talazoparib therapy, with male patients harboring BRCA mutations also demonstrating a favorable response. According to the interim analysis of the TALAPRO-1 trial, the objective response rate (ORR) for the entire patient cohort in the talazoparib treatment group was 25.6%. Among patients with BRCA1/2 mutations, the ORR was higher at 50.0%. Additionally, the trial found that in male patients with prostate cancer harboring BRCA gene alterations, talazoparib delayed disease progression by a median of 11.2 months. Overall, among male patients with a defect in any of 11 DNA repair genes, the median time to disease progression following talazoparib treatment was 5.6 months.

Prostate cancer is the second most common cancer in men, with an incidence rate second only to lung cancer. It is estimated that over 1 million new cases are diagnosed annually. Commenting on these positive findings, lead researcher Johann de Bono, an experimental cancer oncologist at The Institute of Cancer Research, London, stated that the favorable results for talazoparib further demonstrate that PARP inhibitors can delay disease progression and prolong survival in patients with prostate cancer, thereby allowing patients more time with their families.

Beyond prostate cancer, data from talazoparib research presented this year at the American Society of Clinical Oncology (ASCO) indicate that this therapy can also significantly improve the prognosis of breast cancer patients. Results from the NEOTALA clinical trial, which evaluated the efficacy and safety of talazoparib monotherapy as neoadjuvant treatment for HER2-negative locally advanced breast cancer harboring germline BRCA1/2 mutations, demonstrate that talazoparib effectively reduces the risk of recurrence in HER2-negative breast cancer with germline BRCA mutations. Its efficacy is comparable to that of anthracycline-taxane combination regimens, while presenting fewer toxicities and side effects.

Notably, a follow-on Phase III trial for this drug, TALAPRO-2, is also ongoing.

References:

1、Talazoparib emerging as new PARP inhibitor option in prostate cancer

2、New BRCA-targeting drug could treat advanced prostate cancer