P1, N=18, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting

Talazoparib, the strongest PARP-trapping agent, showed markedly greater efficacy than olaparib or veliparib. Combination of talazoparib with exogenous 2'-3'-cyclic GMP-AMP (cGAMP) does not further increase phagocytosis of EwS cells when co-cultured with macrophages, and no additive effects were observed under the tested conditions. Thus, talazoparib is a potent cytotoxic agent with innate immune activation/macrophage-mediated effects, prompting further clinical evaluation in this tumor type.

P3, N=450, Active, not recruiting, Ivy Brain Tumor Center | Recruiting --> Active, not recruiting

We systematically deconstructed the molecular subtypes of primary GISTs by integrated genomic and transcriptomic analysis. A specific GIST subtype characterized by poor treatment responses and prognosis, marked by the activation of aerobic metabolism and HRD features, may be a potential candidate for PARP inhibitors.

In the final PRIMA PRO analysis, results confirmed that niraparib first-line maintenance did not negatively affect HRQOL versus placebo. Disease progression caused sustained HRQOL deterioration across arms, emphasizing the clinical importance of extending progression-free survival to preserve patient HRQOL.

These findings suggest that combining tumor-sensitizing therapies with selective T-cell activation may represent a broader strategy to overcome immune exclusion in solid tumors. Together, these results provide mechanistic rationale for clinical evaluation of olaparib in combination with STAR0602 in patients with mCRPC who have progressed on androgen deprivation therapy.

ATP significantly alleviates olaparib-induced hepatotoxicity by attenuating oxidative stress, suppressing inflammatory responses, restoring antioxidant defense mechanisms and significantly replenishing depleted hepatic ATP levels. These findings suggest that ATP may represent a promising therapeutic strategy for preventing PARP inhibitor-associated drug-induced liver injury.

Furthermore, G73-mediated RAD51 degradation synergizes with the PARP inhibitor olaparib, inducing synthetic lethality and re-sensitizing olaparib-resistant cancers to PARP inhibition. This fully small-molecule-based strategy presents a compelling strategy to overcome resistance to PARP inhibitors, expanding their therapeutic potential beyond patients with HR-deficient tumors.

Although PARP inhibitor olaparib has been approved for metastatic CRPC patients bearing BRCA1/2 mutations, its application is confined to this specific patient subpopulation...Their synergistic effect was confirmed in ex vivo explants from human PCa specimens. Our findings demonstrated CDK9 as a master regulator of BRCAness and proposed targeting CDK9 as a potential strategy to sensitize CRPC patients without BRCA1/2 mutations to PARP inhibition.

P1, N=3, Terminated, University of Iowa | Phase classification: P1/2 --> P1 | Trial completion date: Dec 2024 --> Nov 2025

These data demonstrate that targeting HRD yields promising outcomes in stage III, HER2-negative, HRD breast cancer and that intensified chemotherapy with autologous stem cell rescue does not provide any advantage over state-of-the-art chemotherapy plus olaparib.

P=N/A, N=75, Not yet recruiting, AstraZeneca