Adebrelimab plus chemotherapy as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC): a single-center, phase II, single-arm, open-label clinical trial (ADENEO) protocol

While radical chemoradiotherpy (CRT) is the standard treatment for patients with unresectable locally advanced esophageal squamous cell carcinoma (LA-ESCC), the prognosis remains extremely poor. Although combining CRT with immunotherapy benefits a subset of patients with advanced disease, recurrence and metastasis after treatment are still common. The overall response rate (ORR) of induction chemoimmunotherapy (ICI) for advanced esophageal cancer is approximately 40%-70%. Radiotherapy or concurrent chemoradiotherapy after induction of chemoradiation is more effective. This study aims to tailor subsequent treatment based on the response to ICI to improve therapeutic efficacy for LA-ESCC. The ADENEO trial is a single center, phase II, single-arm, open-label clinical trial that will enroll 60 patients. Eligible patients will be registered, enrolled and receive 2 cycles of adebrelimab plus albumin paclitaxel and carboplatin, and the efficacy will be evaluated. Patients will be divided into two groups according to the efficacy of induction therapy: complete response + partial response (CR + PR) group and stable disease + progression disease (SD + PD) group. In the CR + PR group, patients will be treated with CCRT combined with adebrelimab. The radiotherapy dose is planning target volume (PTV): 50.4 Gy/1.8 Gy/28F. Chemoimmunotherapy will consist of adebrelimab plus albumin-bound paclitaxel and carboplatin, followed by adebrelimab maintenance for up to one year. Patients in the SD + PD group will receive CCRT alone. The radiotherapy dose is PTV/planned gross tumor volume (PGTV): 50.4 Gy/59.92 Gy/28F. The chemotherapy regimen will change to FOLFOX regimen (oxaliplatin, tetrahydrofolic acid and 5-FU) and immunotherapy will not be used during CRT because of tolerance to previous immunotherapy. The primary endpoint is the progression free survival (PFS) assessed by the investigators, and the secondary endpoints are ORR, overall survival (OS), duration of response (DoR), adverse event (AE) and serious adverse time (SAE). Written informed consent will be obtained from all patients enrolled. The study protocol been approved by the Independent Ethical Committee of Tianjin Medical University Cancer Institute & Hospital. The final manuscript will be submitted for publication upon completion of the analysis. ClinicalTrials.gov NCT06452602. Registered 06/11/2024.