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

Introduction: Although 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 CRT combined with immunotherapy has a positive effect on some patients with advanced esophageal cancer, some patients still experience recurrence and metastasis after treatment. The overall response rate (ORR) of induction immunochemotherapy for advanced esophageal cancer is approximately 40%-70%. Radiotherapy or concurrent chemoradiotherapy (cCRT) after induction of chemoradiation is more effective. In this study, different patients were given different treatments according to the therapeutic effect of induction chemoimmunotherapy (ICI) in order to improve the treatment effect of locally advanced esophageal cancer. Methods and analysis: The ADENEO trial is a single center, phase II, single-arm, open-label clinical trial that will enrol 60 patients. Eligible patients will be registered, enrolled and receive 2 cycles of Adebrelimab plus albumin paclitaxel and carboplatin, and the efficacy was evaluated. The patients will divided into complete response + partial response (CR+PR) group and stable disease +progression (SD+PD) group according to the efficacy of induction therapy. In the CR+PR group, patients were treated with concurrent CRT combined with Adebrelimab. Chemoimmunotherapy was the same as that used before, the radiotherapy dose was 50.4Gy/1.8Gy/28F, and immunotherapy was maintained for one year. In the SD+PD group, the patients were treated with cCRT. To further improve the curative effect, the radiotherapy dose was PTV/PGTV: 50.4Gy/59.92Gy/28F. The chemotherapy regimen was changed and immunotherapy was not 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). Ethics and dissemination: Written informed consent will be required from all patients enrolled, and it will be provided by them. The study protocol received approval from the independent ethical review committee of Tianjin Medical University Cancer Institude & Hospital. We will submit the finalised paper for publication on completing the analyses. Trial registration number: NCT06452602 (www.clinicaltrialsregister.eu) (ClinicalTrials.gov).