Adbelimumab Combined With Chemotherapy and Apatinib in Patients With Resectable Esophageal Squamous Cell Carcinoma
NCT Number: NCT06576973
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Esophageal Squamous Cell Carcinoma|Neoadjuvant Treatment
Interventions: DRUG: Adbelimumab, Albumin paclitaxel, Carboplatin, Apatinib|PROCEDURE: Esophagectomy|OTHER: Collecting samples from participant
Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 35
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-08
Completion Date: 2031-12
Locations: 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China

Summary:
Esophageal cancer is a prevalent digestive tract tumor, with around 400,000 new cases and 300,000 deaths globally each year. In the past few decades, surgery, radiotherapy, chemotherapy and other treatments were continuously improved, however, the mortality of esophageal squamous cell carcinoma (ESCC) patients was not significantly decreased. For patients with locally advanced esophageal cancer, direct surgery is not effective. It is difficult to achieve radical resection by surgery merely, and even if many patients receive surgery, they may eventually have tumor recurrence and poor survival rate.

Therefore, it is necessary to explore effective perioperative neoadjuvant treatment to reduce the risk of postoperative recurrence and improve the postoperative survival rate of patients. According to the reports, the expression of PD-L1 in esophageal cancer was about 41.4%. Therefore, PD-1/ PD-L1 immunocheckpoint inhibitor may become a new method for the treatment of ESCC. Preliminary clinical results showed that immunotherapy combined with chemoradiotherapy provided a synergies antitumor effect.

The results of the Phase 1b trial evaluating adbelimumab monotherapy as a neoadjuvant treatment for locally advanced resectable ESCC demonstrated that patients receiving two cycles of neoadjuvant sequential surgery exhibited favorable safety profiles, with no adverse reactions of grade 3 or higher. The trial reported a major pathological response (MPR) rate of 24%, a pathological complete response (pCR) rate of 8%, a 2-year overall survival (OS) rate of 92%, and a 2-year recurrence-free survival (RFS) rate of 100%. The effectiveness of combining adbelizumab with chemotherapy and targeted therapy for locally advanced esophageal cancer is uncertain.

This study aims to assess the efficacy and safety of using adbelizumab with chemotherapy and apatinib as neoadjuvant therapy for resectable ESCC.

Primary Outcome Measures: Pathological Complete Response (PCR), The pCR will be defined as the proportion of participants with absence of residual tumor in the resected primary tumor and all resected lymph nodes after completion of neoadjuvant treatment., 1 month after surgery
Secondary Outcome Measures: Major Pathological Response (MPR), The MPR will be defined as the proportion of participants with less 10% of residual tumor in the resected primary tumor and all resected lymph nodes after completion of neoadjuvant treatment., 1 month after surgery|Objective Response Rate (ORR), The ORR will be defined as the proportion of participants who have a complete response or partial response before surgery as assessed by the investigator per RECIST v1.1 in all participants with measurable disease at baseline, before surgery|The changes in the peripheral blood immunoprofile and tumor tissue sample among non-PCR (NPCR) and PCR patients, By using mass spectrometry (CyTOF) and single-cell analysis, we comprehensively characterized the immune landscape in the peripheral blood and tumor sample of ESCC patients before and after anti-PD-1 immunotherapy, aiming to explore the immune subsets correlated with neoadjuvant immunotherapy response., 3 months after surgery|2-year and 5-year overall survival, The proportion of all study cases in which no death from any cause occurred within 2 years and 5 years after enrolled, 2-year and 5-year after enrolled|Incidence of Treatment-related Adverse Events, Incidence of Treatment-related Adverse Events as Assessed by CTCAE v5.0, 1 month after surgery|R0 resection rate, This will be defined as the proportion of participants with R0 resection, 1 month after surgery