Neoadjuvant Ivonescimab（AK112） Combined With Chemotherapy in Patients With Resectable Esophageal Squamous Cell Carcinoma

NCT07244978 | Not Yet Recruiting Phase 2

• 1 other identifier: 2025-1704
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

In the past few decades, surgery, radiotherapy, chemotherapy and other treatments were continuously improved, however, the mortality of esophageal squamous cell carcinoma patients was not significantly decreased. It is recommended that a treatment strategy be employed that integrates surgery with radiotherapy, chemotherapy, or immunotherapy, in order to enhance overall survival by improving local-regional tumor control and addressing microscopic metastases. Clinical research indicates that combining anti-PD-1/L1 and anti-VEGF antibodies enhances anti-tumor effects in esophageal squamous cell carcinoma. Ivonescimab, a humanized bispecific monoclonal antibody targeting PD-1/VEGF. This single-arm, prospective, exploratory study is planned to evaluate the combination of ivonescimab and chemotherapy in neoadjuvant therapy for resectable esophageal squamous cell carcinoma, with the aim of providing new therapeutic options for this condition.

Conditions

Esophageal Squamous Cell Carcinoma; Neoadjuvant Therapy

Keywords

ivonescimab; anti-PD-1; anti-VEGF; Neoadjuvant; Esophageal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Rate of pathological complete response (PCR)

  The proportion of the surgical population with PCR, which was defined no residual invasive tumor cells were found in the pathological examination of resected specimens, including the primary tumor and lymph nodes.

  1 month after surgery

Secondary Outcomes (5)

• Rate of major pathological response (MPR)

  1 month after surgery

• Rate of objective response rate (ORR)

  before surgery

• 2-year and 5-year overall survival rate

  2-year and 5-year after enrolled

• Incidence of Treatment-related Adverse Events

  1 month after surgery

• The changes in the peripheral blood immunoprofile and tumor tissue sample among non-PCR (NPCR) and PCR patients

  3 month after surgery

Study Arms (1)

Ivonescimab（AK112） Combined With Chemotherapy

EXPERIMENTAL

Preoperative neoadjuvant therapy for 3 cycles. Radical surgery is performed 4-8 weeks after the last dose. Postoperative radiotherapy is determined according to the clinical situation and pathological stage of the patient. Ivonescimab（AK112） can be maintained 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.

Combination Product: Ivonescimab（AK112), Albumin paclitaxel, carboplatin AUC=5, neoadjuvant therapy; Procedure: Esophagectomy; Other: Sample

Interventions

Esophagectomy PROCEDURE

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 Ivor-Lewis (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.

Ivonescimab（AK112） Combined With Chemotherapy

Sample OTHER

Blood, Tumour will be Collected from participant. Fate of sample is Destruction after use. 5 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 during surgery.

Ivonescimab（AK112） Combined With Chemotherapy

Ivonescimab（AK112), Albumin paclitaxel, carboplatin AUC=5, neoadjuvant therapy COMBINATION_PRODUCT

Ivonescimab（AK112) 20mg/kg, IV, Day 1; Albumin paclitaxel 260mg/m2, Day 1; carboplatin AUC=5, Day 1; Preoperative neoadjuvant therapy for 3 cycles, one cycle every 21 days.

Ivonescimab（AK112） 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:

• signed informed consent;
• patients age 18 to 75 years old
• primary resectable, histologically confirmed esophageal squamous cell cancer;
• Esophageal squamous cell carcinoma the clinical stage was II-IVA (according to AJCC TNM stage, 8th edition).
• ECOG PS 0-1.
• No distant metastasis, the diseases could be resectable assessed by thoracic oncologist;

You may not qualify if:

• with significant cardiovascular disease;
• current treatment with anti-viral therapy or HBV;
• Female patients who are pregnant or lactating;
• history of malignancy within 5 years prior to screening;
• active or history of autoimmune disease or immune deficiency;
• signs of distant metastases.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

The Second Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, 310000, China

Location

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Neoadjuvant Therapy; Esophagectomy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Digestive System Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Jianan Wang

  2nd Affiliated Hospital, School of Medicine, Zhejiang University

  STUDY CHAIR

Central Study Contacts

Zixiang Wu, M.D

CONTACT

+8615268156132; zixiang0717@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: November 24, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2032
• Last Updated: April 24, 2026

Record last verified: 2025-11

Locations

CN (1)