NCCN collaborates with Pfizer to advance PARP inhibitors in prostate cancer


The National Comprehensive Cancer Network (NCCN) has awarded approximately $1.5 million in grants to Pfizer Oncology to advance the development of the PARP inhibitor talazoparib (Talzenna) in prostate cancer.1

The grants are targeted to support 2 specific projects:

  • "Intratumor Microdevice to Identify Biomarkers and Pathways Associated with Response to Talazoparib"; primary investigators: Adam Kibel, MD, and Oliver Jonas, PhD, Dana-Farber Brigham Cancer Center
  • "Presurgical Phase II Study of Talazoparib in Combination with Enzalutamide in De Novo Metastatic to Lymph Nodes Prostate Cancer"; primary investigator: Amado Zurita-Saavedra, MD, The University of Texas MD Anderson Cancer Center

"This research will involve innovative investigations of talazoparib and foster the development of PARP inhibitors in prostate cancer," Crystal S. Denlinger, MD, FACP, senior vice president, chief scientific officer, NCCN, stated in a press release. "Congratulations to all of the grantees. We look forward to results that may guide the development of talazoparib alone or in combination with other therapies in prostate cancer."

PARP inhibitor revolution

The 2020 approval of the first PARP inhibitors olaparib (Lynparza) and rucaparib (Rubraca) for prostate cancer patients whose tumors harbor specific genetic alterations was hailed as the dawn of the precision medicine era in prostate cancer.

Specifically, the FDA approved olaparib in May 2020 for the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic mCRPC who have progressed following prior treatment with enzalutamide (Xtandi) or abiraterone acetate (Zytiga). Also in May 2020, the FDA approved rucaparib for the treatment of patients with BRCA mutation (germline and/or somatic)—associated mCRPC who have been treated with androgen receptor–directed therapy and a taxane-based chemotherapy.

The NCCN/Pfizer collaboration and other research in the field is now being aimed at further advancing these agents and launching new PARP inhibitors, such as talazoparib.

Clinical research with talazoparib

The initial promise of talazoparib in prostate cancer was shown in findings from the phase 2 TALAPRO-1 study, which were published in the Lancet Oncology.2 The results showed favorable antitumor activity with talazoparib in heavily pretreated patients with metastatic castration-resistant prostate cancer (mCRPC) and DDR-HRR gene alterations.

At a median follow-up of 16.4 months, the objective response rate (RESIST 1.1) was 29.8% (n = 31) among 104 evaluable patients. The most common gene alterations in this population were BCRA1/2. The confirmed complete response and confirmed partial response rates were 10% and 36% for the BCRA1 or BCRA2 groups, respectively, and 11% and 35%, respectively, for the BCRA2 group.

These results supported additional research, such as the phase 3 TALAPRO-3 study (NCT04821622) evaluating the combination of talazoparib and the antiandrogen agent enzalutamide (Xtandi) in patients with DDR-mutated metastatic castration-sensitive prostate cancer.3

The global, double-blind TALAPRO-3 trial will randomize approximately 550 men to enzalutamide plus either talazoparib or placebo. The study is being conducted at nearly 300 clinical sites spanning 28 countries.

To enroll on the trial, patients must have an ECOG performance status of 0 to 1 and confirmed DDR mutation status through liquid biopsy and/or de novo or archival tumor tissue. Prior therapy is allowed. Patients with brain metastases are not eligible for enrollment. Radiographic progression-free survival is the primary end point of the study, and overall survival is a secondary end point. The estimated primary completion date for the trial is the end of 2024.

Beyond TALAPRO-3, the combination of talazoparib and enzalutamide is also being explored in the ongoing phase 3 randomized, double-blind, placebo-controlled TALAPRO-2 trial (NCT03395197) in patients with mCRPC. DDR defects are not required to enroll.


1. NCCN Announces Funding for Prostate Cancer Research Projects, in Collaboration with Pfizer. Published online December 16, 2021. Accessed January 3, 2022.

2. de Bono JS, Mehra N, Scagliotti GV, et al. Talazoparib monotherapy in metastatic castration-resistant prostate cancer with DNA repair alterations (TALAPRO-1): an open-label, phase 2 trial [published online ahead of print August 10, 2021]. Lancet Oncol. doi: 10.1016/S1470-2045(21)00376-4

3. First Participant Dosed In Pfizer’s Pivotal Phase 3 Talapro-3 Combination Study Of Talazoparib And Enzalutamide In Metastatic Castration-Sensitive Prostate Cancer (MCSPC). Published online June 23, 2021. Accessed January 3, 2022.

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