Talzenna (talazoparib)

Current clinically approved PARP inhibitors (Talazoparib and Olaparib) show outstanding therapeutic capabilities but suffer from severe side effects. These findings identify compound 1a as a promising lead, while compounds 1b and 1c remain viable candidates for further optimization. However, experimental validation is critical to confirm the predicted biological activity and safety profiles.

Functional assays revealed that 58% of PDOs from patients ineligible for US Food and Drug Administration-approved poly(adenosine 5'-diphosphate-ribose) polymerase inhibitors were sensitive to talazoparib, linked to DNA damage repair alterations. Furthermore, combination screens identified agents that overcome resistance, particularly in TP53-mutant models. Our platform enables the investigation of targeted therapies and molecular drivers of drug sensitivity, providing translational insights for personalized treatment beyond current biomarker guidelines.

Agents such as olaparib, talazoparib, and niraparib have demonstrated promising efficacy in both neoadjuvant and adjuvant settings with some trials suggesting that selected patients may avoid chemotherapy. Overall, current evidence supports the role of HRD as a promising biomarker in TNBC. However, further research is required to refine its clinical utility and to integrate HRD testing into personalized treatment strategies, especially in combination with emerging therapies such as immunotherapy.

P3, N=77, Active, not recruiting, Pfizer | Trial completion date: Sep 2026 --> Dec 2026 | Trial primary completion date: Sep 2026 --> Dec 2026

P2, N=33, Recruiting, Alexander B Olawaiye, MD | Trial completion date: Mar 2033 --> Dec 2034 | Trial primary completion date: Dec 2031 --> Nov 2033

Importantly, combining the PI3K/AKT inhibitor PKI-587 with the PARP inhibitor BMN673 synergistically inhibits tumor growth across multiple SCLC models, including cell lines, patient-derived organoids, and xenograft models. Collectively, our findings define a "PI3K/AKT-STAT5A-TRIM21-PARP1" axis critical for SCLC progression and propose its dual inhibition as a promising therapeutic strategy.

In recent years, derivatives of olaparib and rucaparib have been radiolabeled for noninvasive imaging of PARP1 expression and targeted radionuclide therapy of PARP-expressing tumors. Methods for the chiral separation of precursor permitted radiolabeling of [211At]talazoparib without the need for separation from its inactive 211At-labeled enantiomer after radiolabeling, and scaled-up production was optimized. [211At]talazoparib exhibited promising potential as a targeted radiotherapeutic, particularly for settings where locoregional administration is warranted.

Talazoparib added to enzalutamide led to significantly better imaging-based progression-free survival than placebo plus enzalutamide among patients with metastatic APMS prostate cancer harboring alterations in homologous recombination repair genes. Serious adverse events were more common with talazoparib plus enzalutamide than with placebo plus enzalutamide. (Funded by Pfizer; TALAPRO-3 ClinicalTrials.gov number, NCT04821622.).

Current FDA approved drugs and drugs in clinical trials targeted toward the genetic influences of breast cancer include those such as Talazoparib and Margetuximab. Additionally, risk assessment and genetic screening methods are incredibly important to inform patients of their individual risk for breast cancer development. Advancements in understanding of gene specific mechanism and their correlation with breast cancer pathogenesis may provide efficient strategies for precision medicine and enhancing clinical outcomes in breast cancer patients.

Among PARPi, Talazoparib (Talzenna®) is a potent therapy for patients with locally advanced or metastatic BC (mBC) with germline BRCA mutations (gBRCAm) and HER2-negative status, demonstrating the highest potency (IC50 = 0.57 nM), which is 4-10 times lower than that of other PARP inhibitors; olaparib (2.0 nM), rucaparib (1.9 nM), and veliparib (4.7 nM), indicating superior efficacy. The latest advancements in talazoparib research, including all related clinical trials (Phase 1-3) for the treatment of BC, OC, and other solid tumors (STs), are also summarized. A comprehensive analysis of all clinical trials involving talazoparib, whether as monotherapy or in combination with other drugs, elucidates its potential to improve clinical outcomes, address drug resistance, and explore synergistic combinations with other PARPi or novel agents, thereby providing insights into the clinical utility of talazoparib.

P1, N=35, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Sep 2026 --> Dec 2026 | Trial primary completion date: Mar 2026 --> Sep 2025

P1/2, N=90, Recruiting, St. Jude Children's Research Hospital | Trial primary completion date: Dec 2025 --> Dec 2026