Neoadjuvant Ivonescimab and Chemotherapy in Resectable Esophageal Cancer

NCT ID: NCT06814158

Last Updated: 2025-02-07

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-01
• Study Completion Date: 2026-12-31

Brief Summary

Neoadjuvant ChemoRadioTherapy (NCRT) combined with surgical resection is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC) based on CROSS and 5010 study. However, the recurrence and metastasis rate after neoadjuvant therapy is still very high, reaching about 40%, which seriously affects the long-term survival of patients after surgery. Therefore, how to improve the neoadjuvant therapy regimen, thereby increasing the pCR rate of ESCC patients, eliminating micro metastases and prolonging survival, has always been an urgent problem to be solved in clinical practice. The combination of neoadjuvant chemotherapy and immunotherapy significantly improved the perioperative outcomes of ESCC patients, and the safety and efficacy of the chemoimmunotherapy were validated in the population of locally advanced ESCC patients (Keystone 001 and ESCORT-NEO study). The Ivonescimab Injection is an IgG1 subtype humanized bispecific antibody that targets human vascular endothelial growth factor-A (VEGF-A) and programmed death protein-1 (PD-1). It can simultaneously bind to VEGF-A and PD-1, competitively block the interaction between VEGF-A, PD-1 and their ligands, and exert immune and anti angiogenic effects. This innovative antibody structure design effectively reduces the side effects and enhances the safety of the drug therapy. A few clinical trials (HARMONi-A and HARMONi-2study) suggest that the combination therapy of Ivonescimab and chemotherapy for locally advanced ESCC may be safe and effective, and is expected to achieve better therapeutic effects than neoadjuvant chemoimmotherapy. This study aims to explore the safety and efficacy of Ivonescimab combination with chemotherapy in the treatment of locally advanced resectable ESCC (cII-III stage), and analyze the feasibility of this treatment regimen. At the same time, a comprehensive analysis and detection of the tumor immune microenvironment, circulating immune cells, and circulating tumor DNA (ctDNA) in ESCC were conducted to elucidate the role of immune status and dynamic changes in ctDNA for predicting therapeutic efficacy and prognosis.

Conditions

Esophageal Squamour Cell Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant Ivonescimab Combined with Chemotherapy

Ivonescimab 20mg/kg + chemotherapy (Cisplatin + Paclitaxel) Q3W, 3 cycles

Group Type: EXPERIMENTAL

Ivonescimab Combined With Chemotherapy

Intervention Type: DRUG

Ivonescimab 20mg/kg + CT Q3W, 3cycles

Interventions

Ivonescimab Combined With Chemotherapy

Ivonescimab 20mg/kg + CT Q3W, 3cycles

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 1) Histologically confirmed primary esophageal squamous cell carcinoma, locally advanced, staging cT1N2M0, cT2-3N0-2M0 (stage II/III), AJCC 8th edition clinical staging of esophageal squamous cell carcinoma; 2) Surgical treatment is possible; 3) ECOG score: 0 to 1; 4) The function of important organs meets the following requirements (excluding the use of any blood components and cell growth factors within 14 days): the subject has no dysfunction of major organs, and the blood routine, lung, liver, kidney function, and heart function are basically normal. Laboratory laboratory test indicators must meet the following requirements: blood: white blood cells>4.0 × 109/L, absolute count of neutrophils (ANC) ≥ 2.0 × 109/L, platelet count>100 × 109/L, hemoglobin>90g/L; Pulmonary function: FEV1 ≥ 1.2L, FEV1% ≥ 50%, and DLCO ≥ 50%; Liver function: serum bilirubin is below 1.5 times the maximum normal value; ALT and AST are 1.5 times lower than the maximum normal values. Renal function: Blood creatinine (SCr) ≤ 120 µ mol/L, creatinine clearance rate (CCr) ≥ 60 ml/min; 5) Before treatment, gastroscopy tissue and blood samples need to be collected from our center; 6) The subjects voluntarily joined this study, showed good compliance, and cooperated with safety and survival follow-up.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tianjin Medical University Cancer Institute and Hospital

OTHER

Sponsor Role: lead

Responsible Party

Hongjing Jiang

Director of Department Esophageal Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Tianjin Medical University Cancer Hospital

Hexi District, Tianjin Municipality, China

Countries

China

Central Contacts

Hongjing Jiang, MD, PhD

Role: CONTACT

jianghongjing@tmu.edu.cn

022-23340123-6417

Xiaofeng Duan, MD, PhD

Role: CONTACT

xduan@tmu.edu.cn

8613752437179

Facility Contacts

Dongyan Cheng

Role: primary

83951546@qq.com

022-23340123-6012

Other Identifiers

E20241631A

Identifier Type: OTHER

Identifier Source: secondary_id

E20241631A

Identifier Type: -

Identifier Source: org_study_id