Phase 3 Study of Niraparib-Plus-Pembrolizumab as Maintenance Therapy for Advanced/Metastatic Non–Small Cell Lung Cancer (ZEAL-1L)
Mené sur 666 patients atteints d'un cancer du poumon non à petites cellules de stade avancé ou métastatique, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout de niraparib au pembrolizumab en traitement d'entretien
Introduction: This randomized, double-blind, phase 3 study evaluated niraparib-plus-pembrolizumab as maintenance therapy for patients with advanced/metastatic non–small cell lung cancer (NSCLC; ZEAL-1L, ClinicalTrials.gov identifier: NCT04475939).
Methods: Adults with advanced/metastatic squamous/nonsquamous NSCLC without known targetable driver alteration were randomly assigned (1:1) to receive niraparib-plus-pembrolizumab or placebo-plus-pembrolizumab as maintenance therapy. Niraparib was given as a daily oral dose of 300 mg, and intravenous pembrolizumab was administered at 200 mg every 3 weeks. The primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR) in patients with complete or partial response (CR/PR) to front-line chemotherapy combined with pembrolizumab. Hierarchical testing was performed on the primary and key secondary endpoints in a prespecified sequential order; formal testing was stopped if any endpoint failed to reach statistical significance.
Results: Patients comprising the intent-to-treat (ITT) population (n=666) were randomly assigned to niraparib-plus-pembrolizumab (n=331) or placebo-plus-pembrolizumab (n=335) therapy. The median PFS for the CR/PR population (n=200 receiving niraparib-plus-pembrolizumab; n=201 receiving placebo-plus-pembrolizumab) was 5.55 months for both treatment arms (hazard ratio [HR], 1.00; 95% CI, 0.79–1.27; 1-sided p=0.502). Key secondary endpoints of PFS by BICR in the ITT population, overall survival in CR/PR and ITT populations, and time to progression in the central nervous system were not formally tested. The most common grade
≥
3 treatment-related adverse events for the niraparib-plus-pembrolizumab arm were hematologic (anemia, thrombocytopenia, and neutropenia).
Conclusion: The addition of niraparib to pembrolizumab for maintenance therapy in patients with advanced/metastatic NSCLC did not result in improved efficacy; no new safety signals were detected.
Journal of Thoracic Oncology , résumé, 2026