Participants and procedures
intolerable adverse, interstitial lung disease, ESCC, Cancer
CELIAC, DISEASE PROGRESSION, ADVERSE EVENTS, EVENT, AUTOIMMUNE DISEASE, LYMPH NODE METASTASIS, ONCOLOGY, INTERSTITIAL LUNG DISEASE, APPENDIX, CANCER
This clinical trial was exploratory in nature, aiming to investigate the safety and efficacy of socazolimab, and a total of 70 patients (Phase Ib: 6 patients; Phase II: 64 patients) were enrolled based on previous experience. Patients who had histologically or cytologically confirmed ESCC clinically staged as T2N + M0 or T3-4aN ± M0 before treatment and who had no history of antitumor therapy, were 18–75 years old, had an Eastern Cooperative Oncology Group (ECOG) score of 0–1, and could tolerate chemotherapy were eligible for inclusion in our analysis. We excluded ESCC patients who had cervical or combined cervical, supraclavicular, abdominal, retroperitoneal, and pelvic lymph node metastasis; had interstitial lung disease or other preexisting active, possibly recurrent autoimmune disease; or had been treated with corticosteroids (> 10 mg/d prednisone or equivalent) or other immunosuppressants within 2 weeks before the first drug administration. The full eligibility criteria are provided in the study protocol (see Appendix). All patients provided written informed consent prior to enrollment in the study.Sixty-four patients in the Phase II study were randomly divided in a 1:1 ratio between the experimental (Socazolimab + nab-paclitaxel + cisplatin (TP)) and control (Placebo + TP) groups and received four cycles of TP combined with socazolimab or placebo, depending on which group they were in. Socazolimab or placebo was administered to patients intravenously (IV) at a dose of 5 mg/kg at 1 d; nab-paclitaxel was administered at 125 mg/mAll patients underwent video-assisted thoracoscopy esophagectomy (McKeown) 4–6 weeks after neoadjuvant treatment. Two-field lymphadenectomy was performed, including total mediastinal lymph node dissection and bilateral para-laryngeal recurrent nerve lymph node and celiac lymph node dissection. The stomach was dissociated laparoscopically to create a tubular stomach, which was anastomosed through the left neck of the esophageal bed.Enrolled patients were unblinded after the surgery. Five to six weeks postoperatively, adjuvant therapy with socazolimab for 12 cycles or 9 months (whichever came first) was administered to patients in the Socazolimab + TP group who underwent R0 resection but did not achieve pCR, while no further postoperative therapy was administered to patients with R0 resection in the Placebo + TP group (according to the National Comprehensive Cancer Network (NCCN) guidelines). Treatment was discontinued in the event of disease progression, intolerable adverse events, or the investigators' judgment that the risks outweighed the benefits or withdrawal of informed consent.The clinical stages of all participants were determined via cervicothoracic enhanced computer tomography (CT) and ultrasound endoscopy, and 18F-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography (PET)-CT was also performed before and after neoadjuvant treatment. We evaluated the efficacy of neoadjuvant therapy every 2 weeks prior to surgery based on the RECIST v1.1 standard supplemented by the iRECIST standard. Postoperative examinations were conducted at 1 month and then every 3 months following surgery. The reference for adverse events was based on CTCAE5.0 standards.