A phase II, single-centre trial of neoadjuvant toripalimab plus chemotherapy in locally advanced esophageal squamous cell carcinoma

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) remains a challenging malignancy with poor prognosis and limited therapeutic methods. However, recent clinical trials of immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of lethal malignancies. The second-line treatment of late-stage ESCC was approved based on the results of KEYNOTE-180, KEYNOTE-181 and ATTRACTION-1, ATTRACTION-3. Combining ICIs with chemotherapy in neoadjuvant therapy may benefit patients with locally advanced, resectable ESCC. METHODS: A two-arm phase II trial was launched in July 2019 in Henan Cancer Hospital. The primary outcome measure will be completed within 21 months. The pathological complete response (pCR) rate is the primary endpoint, and the secondary endpoints include overall survival (OS), disease-free survival (DFS), the toxicities of the neoadjuvant toripalimab plus chemotherapy, the relationship between combined positivity score (CPS) of specimen and the treatment response, the relationship between lymphocyte infiltration and the treatment response, the progression-free survival (PFS) rate, and adverse events (AEs). It was assumed that the pCR rate of this trial might be 25%. Therefore, the 30 enrolled patients could reject the hypothesis at 75% (α=0.1). DISCUSSION: The study will determine the safety and efficacy of neoadjuvant immunochemotherapy for ESCC and provide enough evidence for phase III clinical trials. TRIAL REGISTRATION: Clinical Trials.gov, NCT03985670, Registered: October 24, 2019, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0008Z9D&selectaction=Edit&uid=U0002MIY&ts=2&cx=-i71o4q. Registry name: “Teripalimab Plus Chemotherapy in Local Advanced Esophageal Cancer”.