Camrelizumab plus nimotuzumab as second-line therapy for advanced esophageal squamous cell carcinoma: a multicenter phase II study.

BACKGROUND: Therapeutic options for advanced esophageal squamous cell carcinoma (ESCC) after first-line failure remain limited, particularly in patients previously exposed to immune checkpoint inhibitors (ICIs). We evaluated the efficacy, safety, and exploratory biomarker correlates of camrelizumab, an ICI, combined with nimotuzumab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, as second-line therapy for ESCC. METHODS: In this multicenter, single-arm, phase II study, patients with advanced ESCC who progressed after first-line therapy received camrelizumab (200 mg every 2 weeks) plus nimotuzumab (400 mg weekly). The primary endpoint was the objective response rate (ORR). RESULTS: Between November 2021 and December 2024, 46 patients were enrolled. The confirmed ORR was 32.6% (15/46; 95% CI 19.5 to 48.0) and the disease control rate was 82.6% (38/46; 95% CI 68.6 to 92.2). Median progression-free survival (PFS) was 9.13 months (95% CI 5.95 to 9.76), and median overall survival (OS) was 12.62 months (95% CI 9.40 to 15.01). Clinical activity was observed across subgroups, including immunotherapy-naïve and previously treated patients (ORR 32.0% vs 33.3%). Patients with EGFR amplification demonstrated a higher ORR (47.1% vs 24.0%) and longer median OS (13.17 vs 9.99 months). Among patients with M1 disease (n=39), the ORR was 30.8% (95% CI 17.0 to 47.6), the median PFS was 8.48 months (95% CI 5.95 to 9.59), and the median OS was 12.55 months (95% CI 7.95 to 14.88). Treatment-related adverse events occurred in 80.4% of patients, with grade ≥3 events in 8.7%. Exploratory analyses suggested that MUC16 mutations were associated with lower ORR (8.3% vs 46.4%, p=0.030), NOTCH3 mutations with prolonged survival (median PFS not reached vs 8.21 months, HR 0.20, p=0.015; median OS not reached vs 10.58 months, HR 0.22, p=0.026), and MTAP deletions with shorter PFS (3.71 vs 9.49 months, HR 3.18, p=0.005). CONCLUSIONS: Camrelizumab combined with nimotuzumab demonstrated encouraging antitumor activity and a manageable safety profile as second-line therapy for advanced ESCC. TRIAL REGISTRATION NUMBER: NCT03766178.