First-line camrelizumab plus pemetrexed and carboplatin for advanced non-squamous non-small-cell lung cancer with brain metastases (CAP-BRAIN): final results of a multicentre, open-label, single-arm, phase 2 trial in China

Summary: Background: The primary analysis of the CAP-BRAIN trial has shown preliminary antitumour activity and safety of first-line camrelizumab plus chemotherapy in patients with advanced non-squamous non-small-cell lung cancer (NSCLC) and brain metastases (BMs). Here, we report the final efficacy analysis of the CAP-BRAIN study following an additional 3-years of follow-up from the data cut-off date of the primary analysis, along with updated safety data. Methods: In this multicentre, open-label, single-arm, phase 2 trial conducted at seven hospitals in China, 45 adult patients with treatment-naive metastatic non-squamous NSCLC and asymptomatic BMs (or intracranial hypertension symptom controlled with dehydration therapy) were treated with four cycles of camrelizumab (200 mg) plus pemetrexed (500 mg/m2) and carboplatin (area under the curve 5). This combination was given intravenously on day 1 of each 21-day cycle. After four cycles, patients received maintenance therapy with camrelizumab and pemetrexed for up to 24 months of camrelizumab, or until disease progression, unacceptable toxicity or death. Primary endpoint was intracranial objective response rate (iORR) in patients with at least one post-baseline tumour assessment (efficacy analysis set). Secondary endpoints were intracranial progression-free survival (iPFS), overall PFS, and overall survival (OS) in all enrolled patients (full analysis set). Both are updated in this final analysis at the end of follow-up. This extended follow-up was not prespecified in the study protocol. This study is registered with ClinicalTrials.gov, NCT04211090. Findings: Between April 13, 2020, and May 12, 2022, 45 (93.8%) of 48 screened patients were enrolled and included in the full analysis set. At data cutoff (May 22, 2025), the median duration of follow-up was 46.7 months (95% confidence interval [CI] 40.7–53.8). The updated confirmed iORR was 57.5% (95% CI 40.9–73.0) in the efficacy analysis set and 51.1% (35.8–66.3) in the full analysis set. The median iPFS was 8.4 months (95% CI 6.2-not reached), and the median overall PFS was 7.2 months (4.5–21.0). The median OS was 18.4 months (95% CI 10.3–29.9). Treatment-related adverse events were reported in 41 (91.1%) of 45 patients. No unexpected safety signals and additional treatment-related deaths were observed. Interpretation: Our final results support the promising benefit and manageable toxicity of first-line camrelizumab plus pemetrexed and carboplatin in non-squamous NSCLC patients with BMs, suggesting the potential for delayed brain radiotherapy in the upfront setting. Further investigation is warranted in a randomised controlled trial. Funding: Jiangsu Hengrui Pharmaceuticals Co., Ltd.