Zejula (niraparib)

P2, N=10, Active, not recruiting, CanariaBio Inc. | Trial completion date: Jul 2025 --> Dec 2027 | Trial primary completion date: Mar 2025 --> Dec 2026

This phase II trial evaluated the efficacy and safety of combining niraparib with the PD-1 inhibitor HX008 in patients with metastatic breast cancer who had germline DNA damage response (DDR) mutations. Somatic TP53 mutations significantly correlated with shorter PFS, while ASXL1 mutations correlated with longer PFS. This chemotherapy-free regimen demonstrates promising efficacy and a tolerable safety profile in patients with metastatic breast cancer and germline DDR mutations, providing a novel therapeutic option for this patient population, even those with brain metastases.

Four PARP inhibitors, olaparib, niraparib, rucaparib, are approved by the Food and Drug Administration (FDA) approved. Despite these advances, selective inhibitors for ARTs remain underexplored. Ongoing research focuses on overcoming PARP inhibitor resistance, improving biomarker-driven patient selection, and expanding therapeutic strategies that target ART-related pathways.

P2, N=32, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed

P2, N=136, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2025 --> Dec 2026

P1/2, N=117, Completed, K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Jan 2026 | Trial primary completion date: May 2025 --> Oct 2025

Pairwise drug combinational antiproliferative assays revealed that 10h and niraparib synergistically enhanced antiproliferative effects against Granta-519. These results suggested that 10h holds promise for further development as a lead compound for the design of ATR kinase-targeted therapies.

P4, N=70, Recruiting, University of Miami | Trial completion date: Mar 2031 --> Jun 2031 | Trial primary completion date: Mar 2029 --> Jun 2029

P1/2, N=22, Completed, NRG Oncology | Active, not recruiting --> Completed

Partial response (PR) was achieved after six cycles of albumin-bound paclitaxel plus carboplatin (nab-TC) combined with bevacizumab (Bev), followed by maintenance therapy with the PARP inhibitor niraparib. This case demonstrates that Bev combined with chemotherapy may be an effective first-line regimen for this rare PTC variant. Maintenance therapy with a PARP inhibitor may prolong progression-free survival.

A2780ADR cells revealed cross‑resistance to multiple compounds, including anticancer drugs [cisplatin (CisPt) and etoposide (Eto)] and DNA repair/DNA damage response (DDR) inhibitors (olaparib, niraparib, entinostat, prexasertib and rabusertib). However, combination treatment with Doxo and Ver also increased the cytotoxic response of non‑malignant murine cardiomyocytes, murine embryonic stem cells and human induced pluripotent stem cells. Taken together, the present study suggested inhibition of MDR1‑mediated Doxo efflux by Ver a useful approach to overcome acquired drug resistance of A2780ADR cells by stimulating DDR‑related cytotoxicity, yet at the price of a potentially increased risk of normal tissue toxicity.