GSK's PARP inhibitor Zejula (niraparib) has demonstrated significant efficacy in patients with mesothelioma, reducing the risk of disease progression or death by 27% in an investigator-led Phase II trial. The findings, presented at the American Association of Cancer Research (AACR) Annual Meeting 2025 in Chicago on April 29, mark an important advancement for patients with this aggressive cancer who have limited treatment options.
The NERO study (NCT05455424) evaluated Zejula in 88 mesothelioma patients who had relapsed following platinum-based systemic therapy. Patients receiving Zejula experienced an average of 1.5 months longer progression-free survival (PFS) compared to those on standard of care treatments.
Professor Gareth Griffiths, director of the Southampton Clinical Trials Unit and co-lead of the trial, emphasized the significance of these results: "Although this increase may seem small, for this group of patients who have very few treatment options and a generally poor prognosis, this is a significant step forward."
"We have shown for the first time that this kind of drug can improve progression-free survival for mesothelioma patients compared with their usual treatment in the NHS. This gives enormous hope to those patients and their families," Griffiths added.
Disease Background and Treatment Landscape
Mesothelioma is a highly aggressive cancer that develops in the protective lining surrounding certain internal organs, most commonly affecting the lungs. The disease is strongly associated with asbestos exposure, with symptoms often appearing decades after initial exposure.
Current standard of care for mesothelioma includes surgery, chemotherapy, radiation therapy, and immunotherapy. However, treatment options remain limited, particularly for patients who relapse after initial therapy, highlighting the significant unmet medical need addressed by the NERO study.
Study Details and Support
The NERO trial was sponsored by the University Hospital Southampton NHS Foundation Trust with funding from Asthma + Lung UK and support from Mesothelioma UK and the Mavis Nye Foundation. The collaborative nature of the study demonstrates the importance of partnerships between healthcare institutions, patient advocacy groups, and industry in advancing treatment options for challenging cancers.
Moving Toward Personalized Medicine
Building on the success of the NERO trial, researchers are now planning a new study called SELECTmeso. This Phase II platform trial will focus on patients with confirmed histological diagnosis of mesothelioma showing evidence of MTAP loss on immunohistochemistry who have experienced disease progression following prior standard systemic therapy.
"This trial will see patients tested for certain biomarkers, or genetic signals, in their tumours and then given the drug that is most likely to work for them," explained Professor Griffiths. "We really hope this step into more personalised medicine could further help these patients who desperately need better treatment options."
PARP Inhibitors in Mesothelioma Treatment
Zejula is an oral poly-ADP ribose polymerase (PARP) inhibitor that received FDA approval in March 2017 for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.
The positive results from the NERO study align with growing interest in PARP inhibition as a therapeutic strategy for mesothelioma. Other PARP inhibitors currently being investigated in this indication include:
- AstraZeneca's Lynparza (olaparib) in a Phase II trial (NCT04515836)
- Pfizer's Talzenna (talazoparib) in a Phase II study (NCT04462809)
Broader Therapeutic Landscape
Beyond PARP inhibition, other novel approaches are being explored for mesothelioma treatment. AstraZeneca is studying volrustomig, a bispecific antibody immunotherapy targeting PD-1 and CTLA-4, currently in Phase III evaluation for malignant pleural mesothelioma (NCT06097728).
In September 2024, the FDA approved MSD's Keytruda (pembrolizumab) in combination with chemotherapy for unresectable advanced or metastatic malignant pleural mesothelioma, based on data from the KEYNOTE-483 study.
The positive results from the NERO trial with Zejula add to this evolving treatment landscape, providing new hope for patients with this challenging malignancy and establishing PARP inhibition as a viable therapeutic approach worthy of further investigation in mesothelioma.
