Camrelizumab Plus Carboplatin and Paclitaxel as First-Line Treatment for Advanced Squamous NSCLC (CameL-Sq): A Phase 3 Trial

Abstract

INTRODUCTION Camrelizumab, a humanized IgG4-κ monoclonal antibody against PD-1, has demonstrated anti-tumor activity and tolerability across various tumors, including lung cancers. We conducted this double-blind, randomized phase 3 trial to investigate the efficacy and safety of camrelizumab or placebo plus chemotherapy as first-line treatment for patients with advanced squamous non-small-cell lung cancer (NSCLC). The predictive value of circulating tumor DNA (ctDNA) dynamics was also analyzed. METHODS CameL-sq, a double-blind, randomized phase 3 trial (NCT03668496), was conducted in 53 centers in China. 389 patients with stage IIIB-IV squamous NSCLC were randomized (1:1) to receive 4-6 cycles of carboplatin plus paclitaxel with camrelizumab or placebo (q3w), followed by maintenance therapy with camrelizumab or placebo. Peripheral blood ctDNA samples were collected at the baseline and the time after two cycles of treatment. RESULTS Of 389 eligible patients, 193 patients allocated camrelizumab plus chemotherapy and 196 patients allocated placebo plus chemotherapy were included in the efficacy and safety analysis. The results showed significantly prolonged progression-free survival (PFS, median, 8·5 vs 4.9 months; p<0.0001) and overall survival (OS, median, not reached vs 14.5 months; p<0.0001) with camrelizumab-chemotherapy versus placebo-chemotherapy. No unexpected treatment/immune-related adverse events were observed in both two groups. Biomarker analysis revealed that ctDNA clearance after two cycles treatment was independently associated with dramatically longer PFS (p<0.0001) and OS (p<0.0001) in camrelizumab plus chemotherapy group. CONCLUSIONS Our findings support camrelizumab plus chemotherapy as a first-line treatment option in advanced squamous NSCLC. On-treatment ctDNA dynamics showed the potent to predict the efficacy of camrelizumab plus chemotherapy.