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

A Prospective, Single-arm, Single-center, Exploratory Study of the Safety and Efficacy of Ivonescimab（AK112） Combined With Chemotherapy in Patients With Resectable Esophageal Squamous Cell Carcinoma

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Neoadjuvant Therapy; Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Procedure: Esophagectomy; Combination product: Ivonescimab（AK112), Albumin paclitaxel, carboplatin AUC=5, neoadjuvant therapy; Other: Sample

Detailed Description

China with high incidence of esophageal cancer, the number of new cases and deaths account for about 50% of the world every year. 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. For patients with locally advanced esophageal squamous cell carcinoma, 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.

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. Consequently, the exploration of effective perioperative adjuvant or neoadjuvant treatment modalities aimed at reducing the risk of postoperative recurrence and enhancing postoperative survival rates is a critical focus in the treatment of esophageal squamous cell carcinoma.

Recently, PD-1/ PD-L1 immunocheckpoint inhibitor may become a new method for the treatment of esophageal cancer. 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, boosts the immune system's anti-tumor response and inhibits VEGF's immunosuppressive effects, enhancing T cell infiltration in tumors. In patients with locally advanced esophageal cancer, the efficacy of ivonescimab combined with chemotherapy for sequential radical surgery is still unclear. Therefore, a 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.

• Study Type: Interventional
• Enrollment (Estimated): 49
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zixiang Wu, M.D; Phone Number: +8615268156132; Email: zixiang0717@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • The Second Affiliated Hospital of Zhejiang University

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: Ivonescimab（AK112） Combined With Chemotherapy; 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.

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 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.; Combination product: Ivonescimab（AK112), Albumin paclitaxel, carboplatin AUC=5, neoadjuvant therapy; 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.; Other: Sample; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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), single-cell analysis, and other detecting techniques , 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 month after surgery
Rate of major pathological response (MPR)	The proportion of the surgical population with MPR, which was defined in the pathological examination of resected specimens, the proportion of residual tumor cells was less than 10%.	1 month after surgery
Rate of objective response rate (ORR)	The proportion of subjects with imaging PR or CR assessed according to RECIST 1.1 criteria	before surgery
2-year and 5-year overall survival rate	The proportion of all study cases in which no death from any cause occurred within 2 years and 5 years after surgery	2-year and 5-year after enrolled

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2032

Study Registration Dates

• First Submitted: November 17, 2025
• First Submitted That Met QC Criteria: November 17, 2025
• First Posted (Actual): November 24, 2025

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: anti-VEGF; Neoadjuvant; Esophageal Squamous Cell Carcinoma; anti-PD-1; ivonescimab
• 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; Therapeutics; Surgical Procedures, Operative; Digestive System Surgical Procedures; Combined Modality Therapy; Neoadjuvant Therapy; Esophagectomy
• Other Study ID Numbers: 2025-1704

Drug and device information, study documents

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