Talzenna (talazoparib)

Platinum resistant ovarian cancer cells were depleted for RPA 1 or 2 and tested for cisplatin, olaparib and talazoparib sensitivity. HAMNO monotherapy was cytotoxic to sensitive and resistant cells. We conclude that RPA directed precision oncology strategy could be a viable strategy in HGSOC.

For HRRm-positive mCRPC, TALA+ENZA provided survival and QALY gains compared with ENZA alone but at higher cost, resulting in an ICER exceeding typical U.S. WTP thresholds.

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

This study developed and validated an LC-MS/MS method for simultaneous quantification of Talazoparib and Enzalutamide in rat plasma using Apalutamide as the internal standard. In pharmacokinetic studies on male Wistar rats, Talazoparib showed a Cmax of 0.88 ng/mL at 3 h and an AUC0-t of 20 ng·h/mL, while Enzalutamide exhibited a Cmax of 76.18 ng/mL at 1 h and an AUC0-t of 1702 ng·h/mL; both had 24 h half-lives. The validated method enables sensitive, rapid, and reliable bioanalysis for preclinical pharmacokinetic evaluation.

Using a GLICO (GLioblastoma Cerebral Organoid) model, we show that MEOX2 knockdown impairs tumor growth and increases sensitivity to temozolomide (TMZ)...Consistent with this, MEOX2-depleted cells exhibit reduced PARylation levels and increased sensitivity to the PARP1 inhibitor Talazoparib, highlighting a potential therapeutic vulnerability. Altogether, our findings reveal a previously unrecognized role for MEOX2 in the DNA damage response of GSCs, particularly in promoting survival and recovery after chemotherapy and ionizing radiation. These results also suggest that MEOX2 functions as a partner of PARP1 and may represent a promising therapeutic target in GBM.

P1, N=93, Completed, Artios Pharma Ltd | N=390 --> 93 | Active, not recruiting --> Completed

P2, N=103, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2025 --> Jan 2027

P1, N=13, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Jan 2027 | Trial primary completion date: Dec 2025 --> Apr 2025

We develop a targeted siRNA nanoparticle delivery system (siLin28B/DSSP@lip-PEG-FA) in combination with the PARP inhibitor BMN673, providing a synergistic therapeutic strategy against MSE...Furthermore, in vitro and in vivo experiments demonstrated that suppression of PARP and LIN28B inhibited vascular leakage and reinforced tight junction integrity. Collectively, our findings highlight dual targeting of PARP and LIN28B as a promising MA management approach in patients with advanced cancers, with the potential to improve patient quality of life.

This study presents an integrated in-silico drug discovery workflow for the identification of new generation analogues of clinically approved drugs Olaparib and Talazoparib as potential PARP1 inhibitors. Overall, this study has underlined the usefulness of integrated in-silico approaches to accelerate the discovery of optimized PARP1 inhibitors for targeted cancer therapy. The online version contains supplementary material available at 10.1007/s40203-025-00543-x.

Using Bayesian evidence synthesis with prespecified borrowing levels, the Japanese subgroup results were compatible in direction and magnitude with the overall TALAPRO-2 effect. These findings reduce uncertainty around local extrapolation; a dedicated randomized study would be required to establish efficacy independently in Japanese patients.

In recurrent ovarian cancer, niraparib+pembrolizumab showed modest activity with durable responses in homologous recombination-deficient (HRD) tumors; olaparib+durvalumab demonstrated high activity in gBRCA platinum-sensitive relapse, and adding bevacizumab broadened benefit in non-BRCA cohorts. In the newly diagnosed disease, rucaparib+nivolumab maintenance failed to improve PFS versus rucaparib alone. Endometrial trials (olaparib+durvalumab; talazoparib+avelumab in mismatch repair-proficient disease) showed limited activity overall, with signals restricted to biomarker-selected subgroups...PARP+PD-1/PD-L1 combinations are most compelling in ovarian cancer, particularly in BRCA/HRD tumors and, in selected settings, with the addition of bevacizumab, while frontline maintenance benefit remains unproven and endometrial activity is modest. Biomarker-guided selection, rational triplets with non-cytotoxic partners, and optimized sequencing warrant further evaluation.