Phase III Study of Niraparib Plus Pembrolizumab as Maintenance Therapy for Advanced or Metastatic NSCLC (ZEAL-1L)

This randomized, double-blind, phase 3 study evaluated niraparib plus pembrolizumab as maintenance therapy for patients with advanced or metastatic NSCLC (NSCLC; ZEAL-1L, ClinicalTrials.gov identifier: NCT04475939).

Adults with advanced or metastatic squamous or nonsquamous NSCLC without a 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 or 200 mg, and intravenous pembrolizumab was administered at 200 mg every 3 weeks. The primary end point was progression-free survival (PFS) by blinded independent central review in patients with a complete or partial response (CR/PR) to front-line chemotherapy combined with pembrolizumab. Hierarchical testing was performed on the primary and key secondary end points in a prespecified sequential order; formal testing was stopped if any end point failed to reach statistical significance.

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 in both treatment arms (hazard ratio, 1.00; 95% confidence interval: 0.79-1.27; 1-sided p = 0.502). Key secondary end points of PFS by blinded independent central review in the ITT population, overall survival in the CR/PR and ITT populations, and time to progression in the central nervous system were not formally tested. The most common grade 3 or higher treatment-related adverse events in the niraparib plus pembrolizumab arm were hematologic (anemia, thrombocytopenia, and neutropenia).

The addition of niraparib to pembrolizumab for maintenance therapy in patients with advanced or metastatic NSCLC did not result in improved efficacy; no new safety signals were detected.

ClinicalTrials.gov Identifier: NCT04475939.