Exploratory study of camrelizumab combined with chemotherapy as second-line treatment for advanced esophageal squamous cell carcinoma

Background: Patients with advanced esophageal squamous cell carcinoma (ESCC) face a poor prognosis and limited options after first-line therapy failure. This study aims to evaluate the efficacy and safety of camrelizumab combined with chemotherapy as a second-line treatment in patients who with or without prior immunotherapy exposure. Method:This single-center, multi-cohorts, phase II exploratory clinical trial enrolled patients with locally recurrent or metastatic ESCC who had either failed or were intolerant to first-line treatment. Patients were stratified into two cohorts: those who had previously received immunotherapy (Cohort 1) and those who had not (Cohort 2). All patients received camrelizumab (Q3W, up to 2 years) combined with nab-paclitaxel or fluorouracil based chemotherapy (Q3W, 4-6 cycles).The primary endpoint was progression-free survival (PFS). Results: Between May 2021 and September 2025, 40 patients were enrolled, with 20 patients in each cohort. The median age was 67 years in Cohort 1 and 66 years in Cohort 2.The median age was 67 years in Cohort 1 and 66 years in Cohort 2. The cohorts comprised 18 (90%) and 15(75%) males;15(75%) and 15(75%) with an ECOG performance status of 1; 10% and 15% with pulmonary metastases; and 55% and 45% with lymph node metastases, respectively. According to RECIST 1.1, among the 15 and 18 evaluable patients in Cohorts 1 and 2, the objective response rate (ORR) was 33.3% and 50.0%, and the disease control rate (DCR) was 93.3% and 88.9%, respectively. The median progression-free survival (mPFS) was 4.5 months(95%CI 2.13-6.8 ) in Cohort 1 and 9.5 months(95%CI 2.7-16.4 ) in Cohort 2. The median overall survival(mOS) was not reached.The most common adverse events (AEs) were lymphocyte count decreased (90% and 75%), anemia (85% and 70%), and decreased neutrophils (50% and 40%), which were grade 1-3. No grade 4 or 5 AEs occurred.The most common immune-related AEs (irAEs) was reactive cutaneous capillary endothelial proliferation(64.% and 57.1%), which was grade 1-2 in all cases. Conclusion: Camrelizumab combined with chemotherapy showed good antitumor efficacy and safety in advanced ESCC as second-line treatment, regardless of whether the patients have previously received immunotherapy.