Esophageal Squamous Cell CarcinomaPhase 2NCT07244978
Neoadjuvant Ivonescimab（AK112） Combined With Chemotherapy in Patients With Resectable Esophageal Squamous Cell Carcinoma
A Phase 2 study testing Ivonescimab（AK112), Albumin paclitaxel, carboplatin AUC=5, neoadjuvant therapy, Esophagectomy and Sample in people with Esophageal Squamous Cell Carcinoma and Neoadjuvant Therapy, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Esophageal Squamous Cell Carcinoma, Neoadjuvant Therapy
- What is being tested?
- Ivonescimab（AK112), Albumin paclitaxel, carboplatin AUC=5, neoadjuvant therapy, Esophagectomy and Sample
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteChina
- Study dates
- 3 Jun 2026to 31 Dec 2032
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The Second Affiliated Hospital of Zhejiang University
Hangzhou, Zhejiang, 310000
Ming Wu, M.D., iwuming22@zju.edu.cn
Hong Shen, M.D., 13362891320, shenhong0023@zju.edu.cn
About this study
Official title: 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.
Read the 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.
- Being tested
- Ivonescimab（AK112), Albumin paclitaxel, carboplatin AUC=5, neoadjuvant therapy, Esophagectomy, Sample
- Keywords
- ivonescimab, anti-PD-1, anti-VEGF, Neoadjuvant, Esophageal Squamous Cell Carcinoma
- Medical subject headings
- Esophageal Squamous Cell Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ivonescimab（AK112), Albumin paclitaxel, carboplatin AUC=5, neoadjuvant therapyCombination 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.
EsophagectomyProcedure or surgery
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.
SampleOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Combination Product: Ivonescimab（AK112), Albumin paclitaxel, carboplatin AUC=5, neoadjuvant therapy; Procedure: Esophagectomy; Other: Sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 month after surgery
Secondary outcomes (5)
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%.
Measured: 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
Measured: 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
Measured: 2-year and 5-year after enrolled
Incidence of Treatment-related Adverse Events
Incidence of Treatment-related Adverse Events as Assessed by CTCAE v5.0
Measured: 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.
Measured: 3 month after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2025
- Study start3 Jun 2026
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Esophageal Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jianan Wang, Study chair, 2nd Affiliated Hospital, School of Medicine, Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07244978
- Sponsor's protocol ID
- 2025-1704
- Status last verified
- Nov 2025
- First submitted
- 17 Nov 2025
- Last updated
- 2 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07244978
- Acronym / sponsor ID
- 2025-1704
- Keywords
- ivonescimab, anti-PD-1, anti-VEGF, Neoadjuvant, Esophageal Squamous Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 49 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- 3 Jun 2026 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2032 (estimated)
- First posted
- 24 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ivonescimab（AK112） Combined With Chemotherapy | Experimental | Combination Product: Ivonescimab（AK112), Albumin paclitaxel, carboplatin AUC=5, neoadjuvant therapy, Procedure: Esophagectomy, Other: SamplePreoperative 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ivonescimab（AK112), Albumin paclitaxel, carboplatin AUC=5, neoadjuvant therapyIvonescimab（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. | Combination product | Ivonescimab（AK112） Combined With Chemotherapy |
| EsophagectomyPrior 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. | Procedure or surgery | Ivonescimab（AK112） Combined With Chemotherapy |
| SampleBlood, 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. | Other | Ivonescimab（AK112） Combined With Chemotherapy |
Primary outcome
Rate of pathological complete response (PCR)
Time frame: 1 month after surgery
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.
5 secondary outcomes
Rate of major pathological response (MPR)
Time frame: 1 month after surgery
Rate of objective response rate (ORR)
Time frame: before surgery
2-year and 5-year overall survival rate
Time frame: 2-year and 5-year after enrolled
Incidence of Treatment-related Adverse Events
Time frame: 1 month after surgery
The changes in the peripheral blood immunoprofile and tumor tissue sample among non-PCR (NPCR) and PCR patients
Time frame: 3 month after surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jianan Wang study chair
2nd Affiliated Hospital, School of Medicine, Zhejiang University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ivonescimab（AK112), Albumin paclitaxel, carboplatin AUC=5, neoadjuvant therapy, Esophagectomy and Sample in people with Esophageal Squamous Cell Carcinoma and Neoadjuvant Therapy, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zixiang Wu, M.D (+8615268156132, zixiang0717@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of pathological complete response (PCR) (time frame: 1 month after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.