A Single-arm, Single-center, Exploratory Clinical Study of Adebrelimab Combined With Neoadjuvant Chemotherapy for the Treatment of Esophageal Squamous Cell Carcinoma
A Single-arm, Single-center, Exploratory Clinical Study of Adebrelimab Combined With Neoadjuvant Chemotherapy for the Treatment of Esophageal Squamous Cell Carcinoma
This study is a prospective, single-arm, phase II exploratory clinical trial. The primary endpoint of this study is to evaluate the pathological complete response (pCR) rate after surgery and to assess the safety of neoadjuvant therapy with adebrelimab combined with platinum-based chemotherapy in patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC) at the Second Qilu Hospital of Shandong University.
The primary endpoint of this clinical trial is the pathological complete response (pCR) rate, defined as the absence of residual viable tumor cells in the resected specimen, including lymph nodes (ypT0N0M0). Secondary endpoints include the major pathological response (MPR) rate, objective response rate (ORR), treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs), as well as quality of life (QOL) assessments during neoadjuvant immunochemotherapy (nICT). MPR is defined as less than 10% residual viable tumor cells in the primary tumor bed following neoadjuvant therapy and resection. ORR represents the percentage of patients achieving complete response (CR) or partial response (PR). Other secondary measures include the tumor downstaging rate, surgery rate, R0 resection rate (defined as no residual tumor at the resection margins), and perioperative complication rate. Furthermore, overall survival (OS) and relapse-free survival (RFS) are considered exploratory endpoints in this study. By evaluating these diverse endpoints, the investigators aim to comprehensively assess the efficacy, safety, and overall impact of the nICT approach in patients with locally advanced resectable ESCC. Additionally, it is planned to construct 20 pairs of esophageal squamous cell carcinoma and adjacent normal esophageal squamous epithelial organoids, laying the groundwork for future in-depth exploration of the mechanisms underlying esophageal carcinogenesis and progression, as well as functional studies of specific genes.
Esophageal cancer (EC) accounted for over 600,000 new cases globally in 2020, establishing its position as one of the most common malignancies worldwide. The majority of EC cases are concentrated in China, where it ranks sixth in incidence and fifth in mortality among all cancer types. Histologically, EC can be primarily classified into two subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Notably, ESCC is the predominant subtype in China, accounting for approximately 90% of patients.
Currently, the standard regimen for treating locally advanced ESCC involves neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant chemotherapy (nCT) followed by esophagectomy, supported by multiple clinical trials. Generally, nCRT is superior to nCT in achieving pathological complete response (pCR). However, patients receiving nCRT exhibit higher recurrence rates and a greater risk of distant metastasis, and surgical complexity increases following chemoradiotherapy. Therefore, novel therapeutic strategies are urgently needed to address these challenges.
In recent years, immune checkpoint inhibitor (ICI) therapy has demonstrated remarkable efficacy in treating various cancers, positioning it as a promising therapeutic agent for managing EC. The favorable outcomes of ICIs in the neoadjuvant treatment of other solid tumors, along with their manageable adverse effects, have sparked growing interest in applying ICIs to the neoadjuvant treatment of EC. This emerging approach holds significant potential in the quest for more effective and well-tolerated treatments for EC.
Multiple clinical trials have investigated the efficacy and safety of immunotherapy in the neoadjuvant treatment of locally advanced resectable EC. A recent meta-analysis indicated that neoadjuvant immunochemotherapy (nICT) is effective and safe in the short term for locally advanced EC, particularly ESCC, and may serve as a reference for future trials. Currently, nICT remains in the clinical trial phase and has not yet been approved for neoadjuvant immunotherapy.
Adebrelimab is a domestically developed humanized anti-PD-L1 monoclonal antibody that has shown promise in cancer treatment. The phase 1b trial NAITON-1907, investigating adebrelimab monotherapy as neoadjuvant treatment for locally advanced resectable ESCC, was published in Nature Medicine (IF=82.9). The study results showed that two cycles of neoadjuvant adebrelimab monotherapy followed by surgery in locally advanced resectable ESCC was well-tolerated, with no grade 3 or higher adverse events. The major pathological response (MPR) rate was 24%, the pathological complete response (pCR) rate was 8%, the 2-year overall survival (OS) rate was 92%, and the 2-year relapse-free survival (RFS) rate reached 100%. This study provides a rationale for neoadjuvant adebrelimab monotherapy in patients with resectable ESCC.
Based on these encouraging results, using adebrelimab combined with chemotherapy as neoadjuvant therapy for locally advanced ESCC holds the potential to enhance anti-tumor efficacy and provide long-term benefits. In this phase II study, we aim to evaluate the efficacy and safety of adebrelimab in combination with platinum plus (nab-)paclitaxel in patients with locally advanced ESCC, exploring the potential of adebrelimab-based neoadjuvant therapy.
This study is a prospective, single-arm, phase II exploratory clinical trial. The primary endpoint of this study is to evaluate the pathological complete response (pCR) rate after surgery and to assess the safety of neoadjuvant therapy with adebrelimab combined with platinum-based chemotherapy in patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC) at the Second Qilu Hospital of Shandong University. The study plans to enroll adult patients aged between 18 and 80 years who have a histopathologically confirmed diagnosis of ESCC. Eligible patients are those with stage II/III disease according to the AJCC/UICC 8th edition Tumor-Node-Metastasis (TNM) staging system, presenting with cT1-3N1-2M0 or cT3-4aN0M0 disease. Exclusion criteria include patients with a history of other uncured malignancies within the past 5 years, individuals with ongoing or a history of autoimmune diseases, and those who have received any prior anti-tumor therapy. This study is to be conducted in accordance with the Declaration of Helsinki (revised in 2013), and informed consent will be obtained from all patients.
The primary endpoint of this clinical trial is the pathological complete response (pCR) rate, defined as the absence of residual viable tumor cells in the resected specimen, including lymph nodes (ypT0N0M0). Secondary endpoints include the major pathological response (MPR) rate, objective response rate (ORR), treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs), as well as quality of life (QOL) assessments during neoadjuvant immunochemotherapy (nICT). MPR is defined as less than 10% residual viable tumor cells in the primary tumor bed following neoadjuvant therapy and resection. ORR represents the percentage of patients achieving complete response (CR) or partial response (PR). Other secondary measures include the tumor downstaging rate, surgery rate, R0 resection rate (defined as no residual tumor at the resection margins), and perioperative complication rate. Furthermore, overall survival (OS) and relapse-free survival (RFS) are considered exploratory endpoints in this study. By evaluating these diverse endpoints, the investigators aim to comprehensively assess the efficacy, safety, and overall impact of the nICT approach in patients with locally advanced resectable ESCC. Additionally, it is planned to construct 20 pairs of esophageal squamous cell carcinoma and adjacent normal esophageal squamous epithelial organoids, laying the groundwork for future in-depth exploration of the mechanisms underlying esophageal carcinogenesis and progression, as well as functional studies of specific genes.
Inclusion Criteria:
Exclusion Criteria:
zhaoyunpengsddx@sdu.edu.cn18766188692