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

Phase 2

Recruiting

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

• Registration Number: NCT06576973
• Lead Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Brief 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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-08
• Study Start: 2024-08-08
• Study First Submitted: 2024-08-25
• Study First Submitted QC: 2024-08-28
• Last Update Submitted: 2024-08-28
• Study First Posted: 2024-08-29
• Last Update Posted: 2024-08-29
• Primary Completion: 2026-12
• Study Completion: 2031-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 35

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Adbelimumab, chemotherapy and apatinib	Adbelimumab, Albumin paclitaxel, Carboplatin, 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.
Adbelimumab, chemotherapy and apatinib	Esophagectomy	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.
Adbelimumab, chemotherapy and apatinib	Collecting samples from participant	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.

Primary Outcome Measures

Name	Time	Method
Pathological Complete Response (PCR)	1 month after surgery	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.

Secondary Outcome Measures

Name	Time	Method
Major Pathological Response (MPR)	1 month after surgery	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.
Objective Response Rate (ORR)	before surgery	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
The changes in the peripheral blood immunoprofile and tumor tissue sample among non-PCR (NPCR) and PCR patients	3 months after surgery	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.
2-year and 5-year overall survival	2-year and 5-year after enrolled	The proportion of all study cases in which no death from any cause occurred within 2 years and 5 years after enrolled
Incidence of Treatment-related Adverse Events	1 month after surgery	Incidence of Treatment-related Adverse Events as Assessed by CTCAE v5.0
R0 resection rate	1 month after surgery	This will be defined as the proportion of participants with R0 resection

Trial Locations

Locations (1)

2nd Affiliated Hospital, School of Medicine, Zhejiang University; 🇨🇳 Hangzhou, China