A Phase 3 clinical trial investigating niraparib plus pembrolizumab (Keytruda) as maintenance therapy for advanced or metastatic non-small cell lung cancer (NSCLC) completed its primary phase on 2025-02-26. The study, NCT04475939, found no significant difference in progression-free survival (PFS) or overall survival (OS) between the combination therapy and pembrolizumab plus placebo, with a hazard ratio of 1.0 for PFS.
Background
Non-small cell lung cancer (NSCLC) is a significant global health challenge. This study investigated maintenance therapy in participants with advanced or metastatic NSCLC who had achieved stable disease, partial response, or complete response following standard of care first-line platinum-based induction chemotherapy with pembrolizumab.
Trial design
The multicenter, randomized, double-blind, placebo-controlled Phase 3 study (NCT04475939) enrolled 666 participants with advanced or metastatic non-small cell lung cancer. Participants were randomized to receive either niraparib plus pembrolizumab or placebo plus pembrolizumab as maintenance therapy.
Key results
Key results from the trial indicate the following:
- Progression-free Survival (PFS) assessed by Blinded Independent Central Review (BICR) in the Complete and Partial Response (CR/PR) population showed a median PFS of 5.55 Months for the Niraparib + Pembrolizumab group and 5.55 Months for the Placebo + Pembrolizumab group.
- In the Intent-to-Treat (ITT) population, median PFS was 4.40 Months for Niraparib + Pembrolizumab and 4.37 Months for Placebo + Pembrolizumab.
- Overall Survival (OS) in the CR/PR population showed a median OS of 24.77 Months for Niraparib + Pembrolizumab and 32.49 Months for Placebo + Pembrolizumab.
- For the ITT population, median OS was 21.36 Months for Niraparib + Pembrolizumab and 25.26 Months for Placebo + Pembrolizumab.
- A Cox proportional hazard analysis for PFS showed a Hazard Ratio (HR) of 1.0 with a 95.0% Confidence Interval of 0.79 to 1.27, and a p-value of 0.502.
- Time to Progression (TTP) in the Central Nervous System (CNS) assessed by BICR using RANO-BM Criteria showed a proportion of participants of 0.11 for Niraparib + Pembrolizumab and 0.10 for Placebo + Pembrolizumab in one measurement, and 0.12 vs 0.11 in another.
What this means
The trial results indicate that adding niraparib to pembrolizumab as maintenance therapy in advanced or metastatic NSCLC did not significantly improve progression-free survival compared to pembrolizumab alone. The median PFS values were nearly identical between the two treatment arms. Furthermore, the overall survival data suggested a numerically lower median OS in the niraparib plus pembrolizumab arm in both the CR/PR and ITT populations, though statistical significance is not provided for OS. The hazard ratio of 1.0 for PFS further supports the conclusion of no added benefit from niraparib in this setting.
Source
The information for this article was sourced from ClinicalTrials.gov, a public database of clinical studies. The trial, NCT04475939, titled "Placebo-controlled Study Comparing Niraparib Plus Pembrolizumab Versus Placebo Plus Pembrolizumab as Maintenance Therapy in Participants With Advanced/Metastatic Non-Small Cell Lung Cancer," completed its primary phase on 2025-02-26, with results posted on clinicaltrials.gov.