487. camrelizumab combined with chemotherapy or apatinib as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma: a phase 2 trial

Abstract Background Increasing evidences prove the encouraging efficacy of neoadjuvant immunochemotherapy for esophageal squamous cell carcinoma (ESCC). However, the safety of chemotherapy is still unsatisfactory. Previous studies have confirmed the good efficacy and tolerance of camrelizumab (PD-1 inhibitor) combined with apatinib (angiogenesis inhibitor) in advanced ESCC. This trial is to assess the effectiveness and safety of camrelizumab plus chemotherapy or apatinib as neoadjuvant therapy for locally advanced ESCC. Here, we reported the results of cohort 2. Methods This is an open-label, non-randomized phase 2 trial of patients with stage cT2-4aN0–3 M0 ESCC. Eligible patients were 18–75 years old, had ECOG PS score of 0–1. Cohort 2 planned to enroll patients with 4 cycles of camrelizumab (200 mg Q2W) and apatinib (250 mg QD). Surgery was performed within 4–6 weeks after neoadjuvant therapy. The primary endpoint was major pathological response (MPR) rate. Secondary endpoints included pathological complete response (pCR) rate, R0 resection rate, disease-free survival, overall survival, and safety. Results Between Feb 2022 and May 2023, 21 patients were enrolled in cohort 2. 14 patients completed neoadjuvant therapy, the ORR was 50% and the DCR was 100%. 14 patients completed surgery and all patients (100%) reached R0 resection, 4 patients (4/14, 28.6%) reached MPR, 2 patients (2/14, 14.3%) reaching pCR, and 9 patients (9/14, 64.3%) had TNM downstaging. Any grade and grade ≥ 3 adverse events occurred in 84.2% and 9.5% of 21 patients, respectively. The most common AEs were thrombocytopenia (6/21, 28.6%) and increased alanine aminotransferase (6/21, 28.6%). No new safety signals or treatment-related deaths were observed. Conclusions Neoadjuvant camrelizumab in combination with apatinib in patients with locally advanced ESCC showed promising pathological response and downstaging effect with acceptable security. The study enrollment is ongoing, and further survival and safety data will be reported in the future.