Adbelimumab Combined With Chemotherapy and Apatinib in Patients With Resectable Esophageal Squamous Cell Carcinoma

A Prospective, Single-arm, Single-center, Exploratory Study of the Safety and Efficacy of Adbelimumab Combined With Chemotherapy and Apatinib in Patients With Resectable Esophageal Squamous Cell Carcinoma

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.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Squamous Cell Carcinoma; Neoadjuvant Treatment
• Intervention / Treatment: Drug: Adbelimumab, Albumin paclitaxel, Carboplatin, Apatinib; Procedure: Esophagectomy; Other: Collecting samples from participant

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ming Wu, M.D; Phone Number: +8613757118715; Email: iwuming22@zju.edu.cn

Study Locations

• China
  • China
    • Hangzhou, China, China, 310009
      • Recruiting
      • 2nd Affiliated Hospital, School of Medicine, Zhejiang University
      • Contact: Ming Wu, M.D; Phone Number: +8613757118715; Email: iwuming22@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed informed consent.
2. Patients age 18 to 75 years old.
3. Primary resectable, histologically confirmed esophageal squamous cell cancer.
4. Esophageal squamous cell carcinoma the clinical stage was II-IVA (according to AJCC TNM stage, 8th edition).
5. ECOG PS 0-1.
6. No distant metastasis, the diseases could be resectable assessed by thoracic oncologist.

Exclusion Criteria:

1. With significant cardiovascular disease.
2. Current treatment with anti-viral therapy or HBV.
3. Female patients who are pregnant or lactating.
4. History of malignancy within 5 years prior to screening.
5. Active or history of autoimmune disease or immune deficiency.
6. Signs of distant metastases.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Adbelimumab, chemotherapy and apatinib; Preoperative neoadjuvant therapy for 4 cycles. Radical surgery is performed 4-6 weeks after the last dose. Postoperative radiotherapy is determined according to the clinical situation and pathological stage of the patient. Adbelimumab can be aintained for a maximum of 1 year. During the study, patients were be followed until disease progression, withdrawal of informed consent, loss of follow-up, or death.

Drug: Adbelimumab, Albumin paclitaxel, Carboplatin, Apatinib; Adbelimumab 1200mg Day 1; Albumin paclitaxel 260mg/m2, Day 1; carboplatin AUC=5, Day 1; Apatinib 250mg Po Day 2-4. Preoperative neoadjuvant therapy for 4 cycles, one cycle every 21 days.; Other Names: Esophagectomy; Procedure: Esophagectomy; Prior to each surgical procedure, the department engaged in comprehensive discussions and deliberations to ascertain and establish the most suitable course of action. Minimally invasive IvorLewis (intrathoracic anastomosis) or McKeown (neck anastomosis) esophagectomy, including two field extensive lymphadenectomies, was performed according to the tumor location. The resection length should be at least 5cm from the tumor origin according to prechemotherapy by endoscopy. The surgeries will be performed by surgeons with rich experience. Minimally invasive esophagectomy, can be performed using the da Vinci surgical robot, thoracoscope, or laparoscope, or by using an open approach, as judged appropriate by the surgeon.; Other: Collecting samples from participant; Blood, Tumour will be Collected from participant. Fate of sample is Destruction after use. 20 ml of peripheral blood was collected the day before each of the immunotherapy sessions and after surgery. Tumour sample will be collected before neoadjuvant therapy and after surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-related Adverse Events	Incidence of Treatment-related Adverse Events as Assessed by CTCAE v5.0	1 month after 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
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
R0 resection rate	This will be defined as the proportion of participants with R0 resection	1 month after surgery

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Study Chair: Wang, 2nd Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2031

Study Registration Dates

• First Submitted: August 25, 2024
• First Submitted That Met QC Criteria: August 28, 2024
• First Posted (Actual): August 29, 2024

Study Record Updates

• Last Update Posted (Actual): December 2, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Apatinib; Chemotherapy; Esophageal Squamous Cell Carcinoma; Neoadjuvant Treatment; Adbelimumab
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Organic Chemicals; Surgical Procedures, Operative; Coordination Complexes; Digestive System Surgical Procedures; Carboplatin; apatinib; Esophagectomy
• Other Study ID Numbers: 2024-0949

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No