Efficacy, Safety, and Health-Related Quality of Life With Camrelizumab Plus Pemetrexed and Carboplatin as First-Line Treatment for Advanced Nonsquamous NSCLC With Brain Metastases (CAP-BRAIN): A Multicenter, Open-Label, Single-Arm, Phase 2 Study

Introduction: Systemic treatment options for NSCLC with brain metastases (BMs) are scarce. We evaluated the tivity and safety of camrelizumab plus chemotherapy first-line therapy in patients with advanced nonsquamous NSCLC with BMs. Methods: This was a multicenter, single-arm, phase 2 trial (NCT04211090) conducted at seven hospitals in China. Eligible patients had treatment-naive metastatic non-squamous NSCLC and BMs that were asymptomatic symptoms controlled with dehydration therapy and previous systemic treatment or local therapy for the target brain lesion. Patients received camrelizumab (200 mg) plus pemetrexed (500 mg/m2) and carboplatin (area under curve 5) intravenously on day 1 of each 21-day cycle four cycles, followed by maintenance with camrelizumab (200 mg) and pemetrexed (500 mg/m2) every 21 days until disease progression, unacceptable toxicity, or death. The primary end point was confirmed intracranial objective response rate according to modified Response Evaluation Criteria in Solid Tumors version 1.1, which was primarily analyzed in the efficacy analysis set (EAS). Results: A total of 45 patients were enrolled and treated (full analysis set), with 40 patients having at least one post- baseline tumor assessment (EAS). As of August 30, 2022, median follow-up duration was 12.5 months (95% confi- dence interval [CI]: 9.2-17.3). The confirmed intracranial objective response rate was 52.5% (95% CI: 36.1-68.5) in EAS and 46.7% (95% CI: 31.7-62.1) in full analysis set. The extracranial objective response rate was 47.5% (95% CI: 31.5-63.9) and 42.2% (95% CI: 27.7-57.8), respectively. Median intracranial progression-free survival was 7.6 months (95% CI: 4.6-not reached [NR]), median overall progression-free survival was 7.4 months (95% CI: 4.4-NR), and median overall survival was 21.0 months (95% CI: 15.9-NR). The most common treatment-related adverse events of grade 3 or higher were neutrophil count decrease (six [13.3%]) and anemia (four [8.9%]). One treatment- related death occurred owing to immune-related pneu- monia. Linear mixed-effects model displayed that a positive trend for improvement in cognitive function and quality of life was observed based on Montreal Cognitive Assessment and Functional Assessment of Cancer Therapy-Lung scores (p 1/4 0.025, p < 0.001). Conclusions: Camrelizumab plus pemetrexed and carbo- platin was found to have an activity with manageable toxicity and to improve cognitive function and quality of life for patients with nonsquamous NSCLC with BMs in the first- line setting.

Automated summary

This multicenter, single-arm, phase 2 trial evaluated the efficacy and safety of camrelizumab plus chemotherapy as a first-line therapy for advanced nonsquamous NSCLC with brain metastases. The results showed that this treatment regimen had manageable toxicity and improved cognitive function and quality of life in patients with nonsquamous NSCLC with brain metastases.