Zejula (niraparib)

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.

P1, N=42, Active, not recruiting, Nader Sanai | Trial completion date: Sep 2025 --> Mar 2027

Consequently, pharmacological inhibition of CDK4/6 downregulated MCM2/5 expression and, when combined with niraparib, synergistically suppressed NirR tumor growth both in vitro and in vivo. Our findings identify the MCM2/5 complex as a critical mediator of PARPi resistance and establish the therapeutic potential of combining PARPis with CDK4/6 inhibitors to overcome this resistance in ovarian cancer.

No cases of myelodysplastic syndrome or acute myeloid leukemia were observed. In this large multicenter real-world cohort, first-line maintenance therapy with olaparib and niraparib provided durable PFS benefit in patients with advanced EOC, particularly among those with pathogenic BRCA mutations, confirming their effectiveness and manageable safety profiles in routine clinical practice.

Overall, the results indicate that maintaining Abiraterone treatment in combination with PARPis after resistance develops provides superior therapeutic efficacy compared to PARP inhibition alone, offering a promising strategy for managing Abiraterone-resistant prostate cancer. Combining Abiraterone with PARPis enhances therapeutic efficacy and overcomes the acquired insensitivity in mCRPC with BRCA1/2 or HRR mutations. These results support continued use of PARPis with Abiraterone to improve clinical outcomes.