Neoadjuvant Ivonescimab and Chemotherapy in Resectable Esophageal Cancer

NCT06814158 | Not Yet Recruiting Phase 2

• 1 other identifier: E20241631A
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

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

Keywords

Esophageal cancer; Squamous cell carcinoma; Neoadjuvant therpay; VEGF-A; PD-1; Immunotherapy; Ivonescimab

Outcome Measures

Primary Outcomes (1)

• pathological complete response, pCR

  From enrollment to the postoperative pathology report at 6 weeks

Study Arms (1)

Neoadjuvant Ivonescimab Combined with Chemotherapy

EXPERIMENTAL

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

Drug: Ivonescimab Combined With Chemotherapy

Interventions

Ivonescimab Combined With Chemotherapy DRUG

Ivonescimab 20mg/kg + CT Q3W, 3cycles

Neoadjuvant Ivonescimab Combined with Chemotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) 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.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Tianjin Medical University Cancer Hospital

Hexi District, Tianjin Municipality, 300060, China

Location

MeSH Terms

Conditions

Esophageal Neoplasms; Carcinoma, Squamous Cell

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Hongjing Jiang, MD, PhD

CONTACT

022-23340123-6417; jianghongjing@tmu.edu.cn

Xiaofeng Duan, MD, PhD

CONTACT

8613752437179; xduan@tmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department Esophageal Surgery

Study Record Dates

• First Submitted: February 3, 2025
• First Posted: February 7, 2025
• Study Start: March 1, 2025
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 7, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)