Zejula (niraparib)

P1, N=161, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027

P1, N=8, Completed, OHSU Knight Cancer Institute | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Jun 2025

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

Post-recurrence, she received off-label maintenance with tamoxifen 20 mg daily for five years and remains disease-free at 70 months...Postoperative chemotherapy with carboplatin-paclitaxel was followed by maintenance niraparib 100 mg twice daily for three years...Complete cytoreductive surgery combined with tailored systemic and maintenance therapies can achieve sustained remission even in advanced-stage BRCA-wild-type patients. Broader molecular profiling and international collaboration are essential to refine management strategies for this rare and aggressive malignancy.

PRO-based surveillance showed satisfactory QOL and stable symptom control in PSROC after long-term period of niraparib maintenance, regardless of BRCA status. This real-world research highlights the significance of long-term usage of niraparib and PROs in PSROC management.

ZDHHC12 knockdown restores PARP1 trapping and resensitizes resistant cells and xenografts to Niraparib. These findings establish ZDHHC12-mediated PARP1 palmitoylation as a targetable vulnerability to overcome PARPi resistance.

P2, N=20, Active, not recruiting, Massachusetts General Hospital | Trial primary completion date: Dec 2025 --> Dec 2026

P1/2, N=46, Active, not recruiting, University of Alabama at Birmingham | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Nov 2026 --> Nov 2027

Here we show that combination of niraparib and lenvatinib exhibits significant synergistic inhibitory effects against platinum-resistant OCCC cell lines, xenografts, patient-derived tumoroid (PDT) models, and prolonged survival in the platinum-refractory patient-derived xenograft (PDX) model. RNA sequencing revealed that the most differentially expressed genes in PDX models treated with this combination were associated with structural ribosomal components. This combination suppresses Src phosphorylation, NPM1 expression, and ribosomal protein levels in OCCC.

P1/2, N=272, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed

Of all trials, only MAGNITUDE, evaluating niraparib and abiraterone, led to aligned conclusions from both the EMA and FDA, as its design effectively identified the subgroup most likely to benefit. Currently, there is a need for harmonisation in biomarker-driven trial designs and the definition of homologous recombination repair deficiency (HRD). Access to biomarker and clinical data from all PARP-inhibitor trials would allow researchers to clarify the impact of different HRR mutations on outcomes.

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.