This is a prospective, multi-cohort, exploratory clinical study designed to evaluate the efficacy and safety of neoadjuvant adebrelimab combined with chemotherapy in patients with resectable locally advanced thoracic esophageal squamous cell carcinoma (ESCC), with a particular focus on the effect of the time-of-day of immunotherapy infusion.
Eligible patients with histologically or cytologically confirmed, resectable locally advanced thoracic ESCC will be randomly assigned in a 1:1:1 ratio to three cohorts according to predefined immunotherapy infusion time windows. Cohort A will receive adebrelimab plus chemotherapy with the first cycle initiated at or after 15:00 and subsequent cycles initiated before 15:00; Cohort B will receive all three cycles initiated before 15:00; and Cohort C will receive all three cycles initiated at or after 15:00. Neoadjuvant treatment consists of three cycles of adebrelimab in combination with nab-paclitaxel and cisplatin, followed by surgical resection 4-6 weeks after completion of neoadjuvant therapy.
The primary endpoint of the study is pathological complete response (pCR). Secondary endpoints include event-free survival (EFS), major pathological response (MPR) rate, R0 resection rate, overall survival (OS), and disease-free survival (DFS).
Tumor response will be assessed according to RECIST version 1.1, and pathological response will be evaluated using the College of American Pathologists (CAP) tumor regression grading system and AJCC 8th edition staging criteria. Safety will be continuously monitored throughout the study, and patients will undergo scheduled follow-up for disease progression or recurrence and survival after completion of study treatment.
Patients who have signed a written informed consent form and voluntarily agree to participate in the study.
Histologically or cytologically confirmed esophageal squamous cell carcinoma.
Tumor located in the thoracic esophagus, assessed by CT, MRI, EUS, or other imaging modalities, with clinical stage T1b-4aN+M0 or T2-4N0M0 (T2N0 patients must have high-risk features: lymphovascular invasion [LVI], tumor ≥3 cm, or poor differentiation) according to AJCC 8th edition.
Tumors deemed potentially resectable with R0 margins.
Tumor with obvious invasion of adjacent critical structures, such as the aorta or trachea.
Presence of supraclavicular lymph node metastasis.
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
Poor nutritional status with body mass index (BMI) <18.5 kg/m²; patients whose nutritional status is corrected before randomization through supportive care may be considered eligible at the discretion of the principal investigator.
Tang-Du Hospital
Lead sponsor