Nivolumab plus ipilimumab with chemotherapy for non–small cell lung cancer with untreated brain metastases: A multicenter single-arm phase 2 trial (NIke, LOGiK 2004)

Abstract

BackgroundThe effect of dual immunotherapy combined with platinum-based chemotherapy on untreated brain metastases derived from non–small cell lung cancer (NSCLC) has remained unclear. MethodsThis multicenter single-arm phase 2 study enrolled patients with chemotherapy-naïve advanced NSCLC and at least one brain metastasis ≥ 5 mm in size that had not been previously treated. Patients received nivolumab plus ipilimumab combined with platinum-doublet chemotherapy (two cycles), followed by nivolumab-ipilimumab alone. The primary endpoint of the study was intracranial response rate as determined by modified Response Evaluation Criteria in Solid Tumors (RECIST) for brain metastases of ≥ 5 mm as target lesions. ResultsA total of 30 patients from 18 institutions was enrolled in this study. The median age was 66.5 years (range, 47–83 years), and 26 patients (87 %) had a non–squamous cell carcinoma histology. The median size of all target brain lesions was 8.4 mm, with a range of 5–39 mm. The intracranial response rate assessed by modified RECIST was 50.0 % (95 % CI, 33.2–66.8 %), with the rate of complete response being 20.0 %, and the study met its primary endpoint. The systemic response rate was 53.3 % (95 % CI, 36.1–69.8 %), and responses for intracranial and extracranial lesions were generally consistent. The median intracranial progression-free survival was 8.1 months, and both the median intracranial duration of response and time to brain radiotherapy were not reached. ConclusionNivolumab plus ipilimumab combined with platinum-based chemotherapy showed promising intracranial activity in NSCLC patients with untreated brain metastases. Trial registrationjRCT071210019.