Esophageal Squamour Cell CancerPhase 2NCT06814158
Neoadjuvant Ivonescimab and Chemotherapy in Resectable Esophageal Cancer
A Phase 2 study testing Ivonescimab Combined With Chemotherapy in people with Esophageal Squamour Cell Cancer, run by Tianjin Medical University Cancer Institute and Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Esophageal Squamour Cell Cancer
- What is being tested?
- Ivonescimab Combined With Chemotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 1 siteChina
- Study dates
- 1 Mar 2025to 31 Dec 2026
- 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
- 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.
Who cannot join
- 1) Previously received radiation therapy, chemotherapy, hormone therapy, surgery, or molecular targeted therapy; 2) Suspected cervical lymph node metastasis on imaging; The subject has a history or concurrent history of other malignant tumors (Excluding cured basal cell carcinoma of the skin and cervical carcinoma in situ; 3) Previous PD-1/PD-L1 treatment history; 4) History of allergies to macromolecular protein preparations or any PD-1 components; 5) Subjects with any active autoimmune disease or history of autoimmune disease (such as but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism; subjects with vitiligo or complete remission of childhood asthma without any intervention in adulthood; subjects with asthma requiring medical intervention with bronchodilators cannot be included); 6) The subject is currently using immunosuppressive agents, systemic or absorbable local hormone therapy to achieve immunosuppressive effects (dose>10mg/day prednisone or other therapeutic hormones), and has continued to use them within 2 weeks prior to enrollment; 7) Ascites or pleural effusion with clinical symptoms require therapeutic puncture or drainage; 8) Patients with uncontrolled cardiac clinical symptoms or diseases, such as: (1) NYHA grade 2 or above heart failure, (2) unstable angina, (3) myocardial infarction within 1 year, and (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; 9) Abnormal coagulation function (PT>16s, APTT>43s, TT>21s, Fbg>2g/L), with bleeding tendency or undergoing thrombolytic or anticoagulant therapy; 10) The patient currently (within 3 months) has digestive tract diseases such as esophageal varices, active ulcers in the stomach and duodenum, ulcerative colitis, portal hypertension, or active bleeding from unresected tumors, or other conditions determined by the researchers that may cause gastrointestinal bleeding or perforation; 11) Previous or current severe bleeding (bleeding>30 ml within 3 months), hemoptysis (fresh blood >5ml within 4 weeks) or thromboembolic events (including stroke events and/or transient ischemic attacks) occurring within 12 months; 12) The subject has an active infection or an unexplained fever >38.5℃ during the screening period or before the first administration (according to the researcher's judgment, subjects with fever caused by tumors can be included in the group); 13) Having experienced abdominal fistula, gastrointestinal perforation, or abdominal abscess less than 4 weeks prior to medication; 14) Patients with objective evidence of past and current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severe impairment of lung function, etc; 15) Subjects with congenital or acquired immune function defects, such as HIV infection, or active hepatitis (transaminase does not meet the inclusion criteria, hepatitis B reference: HBV DNA ≥10^4/ml ; Hepatitis C reference: HCVRNA≥10^3/ml); Chronic hepatitis B virus carriers with HBV DNA<2000 IU/ml (<10^4 copies/ml) must receive antiviral treatment during the trial period in order to be enrolled; 16) The subjects are currently participating in other clinical studies or have been less than one month since the end of the previous clinical study; Participants may receive other systemic anti-tumor treatments during the study period; 17) Medication less than 4 weeks before the study or may receive live vaccine during the study period; 18) The subject is known to have a history of substance abuse, alcoholism, or drug use; 19) The subject is unable or unwilling to bear the self funded portion of the examination and treatment costs; 20) The researchers believe that the subjects should be excluded from this study, for example, if the researchers determine that there are other factors that may cause the study to be terminated midway, such as other serious illnesses (including mental illnesses) that require concomitant treatment, serious laboratory abnormalities, accompanied by family or social factors, which may affect the safety of the subjects, or the collection of data and samples.
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
Tianjin Medical University Cancer Hospital
Hexi District, Tianjin Municipality, 300060
Dongyan Cheng, 022-23340123-6012, 83951546@qq.com
About this study
Official title: A Phase II Study of Neoadjuvant Ivonescimab Combined with Chemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma
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
- Being tested
- Ivonescimab Combined With Chemotherapy
- Keywords
- Esophageal cancer, Squamous cell carcinoma, Neoadjuvant therpay, VEGF-A, PD-1, Immunotherapy, Ivonescimab
- Medical subject headings
- Esophageal Neoplasms, Carcinoma, Squamous Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ivonescimab Combined With ChemotherapyDrug
Ivonescimab 20mg/kg + CT Q3W, 3cycles
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant Ivonescimab Combined with Chemotherapy | Experimental | Ivonescimab 20mg/kg + chemotherapy (Cisplatin + Paclitaxel) Q3W, 3 cycles Receives: Drug: Ivonescimab Combined With Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
pathological complete response, pCR
Measured: From enrollment to the postoperative pathology report at 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2025
- Study start1 Mar 2025 (estimated)
- Primary completion30 Jul 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Esophageal Squamour Cell CancerStudies of the same condition, open and under way.
- More trials run by Tianjin Medical University Cancer Institute and HospitalThe 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 57 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hongjing Jiang, Tianjin Medical University Cancer Institute and Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06814158
- Sponsor's protocol ID
- E20241631A
- Other IDs
- E20241631A
- Status last verified
- Jan 2025
- First submitted
- 3 Feb 2025
- Last updated
- 7 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD will be shared based on the request from other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Neoadjuvant Ivonescimab Combined with Chemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT06814158
- Acronym / sponsor ID
- E20241631A
- Conditions
- Esophageal Squamour Cell Cancer
- Keywords
- Esophageal cancer, Squamous cell carcinoma, Neoadjuvant therpay, VEGF-A, PD-1, Immunotherapy, Ivonescimab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 57 participants (estimated)
- Lead sponsor
- Tianjin Medical University Cancer Institute and HospitalUniversity, hospital or other
- Study start
- 1 Mar 2025 (estimated)
- Primary completion
- 30 Jul 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 7 Feb 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant Ivonescimab Combined with Chemotherapy | Experimental | Drug: Ivonescimab Combined With ChemotherapyIvonescimab 20mg/kg + chemotherapy (Cisplatin + Paclitaxel) Q3W, 3 cycles |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- 1) Previously received radiation therapy, chemotherapy, hormone therapy, surgery, or molecular targeted therapy; 2) Suspected cervical lymph node metastasis on imaging; The subject has a history or concurrent history of other malignant tumors (Excluding cured basal cell carcinoma of the skin and cervical carcinoma in situ; 3) Previous PD-1/PD-L1 treatment history; 4) History of allergies to macromolecular protein preparations or any PD-1 components; 5) Subjects with any active autoimmune disease or history of autoimmune disease (such as but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism; subjects with vitiligo or complete remission of childhood asthma without any intervention in adulthood; subjects with asthma requiring medical intervention with bronchodilators cannot be included); 6) The subject is currently using immunosuppressive agents, systemic or absorbable local hormone therapy to achieve immunosuppressive effects (dose>10mg/day prednisone or other therapeutic hormones), and has continued to use them within 2 weeks prior to enrollment; 7) Ascites or pleural effusion with clinical symptoms require therapeutic puncture or drainage; 8) Patients with uncontrolled cardiac clinical symptoms or diseases, such as: (1) NYHA grade 2 or above heart failure, (2) unstable angina, (3) myocardial infarction within 1 year, and (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; 9) Abnormal coagulation function (PT>16s, APTT>43s, TT>21s, Fbg>2g/L), with bleeding tendency or undergoing thrombolytic or anticoagulant therapy; 10) The patient currently (within 3 months) has digestive tract diseases such as esophageal varices, active ulcers in the stomach and duodenum, ulcerative colitis, portal hypertension, or active bleeding from unresected tumors, or other conditions determined by the researchers that may cause gastrointestinal bleeding or perforation; 11) Previous or current severe bleeding (bleeding>30 ml within 3 months), hemoptysis (fresh blood >5ml within 4 weeks) or thromboembolic events (including stroke events and/or transient ischemic attacks) occurring within 12 months; 12) The subject has an active infection or an unexplained fever >38.5℃ during the screening period or before the first administration (according to the researcher's judgment, subjects with fever caused by tumors can be included in the group); 13) Having experienced abdominal fistula, gastrointestinal perforation, or abdominal abscess less than 4 weeks prior to medication; 14) Patients with objective evidence of past and current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severe impairment of lung function, etc; 15) Subjects with congenital or acquired immune function defects, such as HIV infection, or active hepatitis (transaminase does not meet the inclusion criteria, hepatitis B reference: HBV DNA ≥10^4/ml ; Hepatitis C reference: HCVRNA≥10^3/ml); Chronic hepatitis B virus carriers with HBV DNA<2000 IU/ml (<10^4 copies/ml) must receive antiviral treatment during the trial period in order to be enrolled; 16) The subjects are currently participating in other clinical studies or have been less than one month since the end of the previous clinical study; Participants may receive other systemic anti-tumor treatments during the study period; 17) Medication less than 4 weeks before the study or may receive live vaccine during the study period; 18) The subject is known to have a history of substance abuse, alcoholism, or drug use; 19) The subject is unable or unwilling to bear the self funded portion of the examination and treatment costs; 20) The researchers believe that the subjects should be excluded from this study, for example, if the researchers determine that there are other factors that may cause the study to be terminated midway, such as other serious illnesses (including mental illnesses) that require concomitant treatment, serious laboratory abnormalities, accompanied by family or social factors, which may affect the safety of the subjects, or the collection of data and samples.
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 Combined With ChemotherapyIvonescimab 20mg/kg + CT Q3W, 3cycles | Drug | Neoadjuvant Ivonescimab Combined with Chemotherapy |
Primary outcome
pathological complete response, pCR
Time frame: From enrollment to the postoperative pathology report at 6 weeks
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 7 Feb 2025.
- Individual participant dataSharing planned: No. IPD will be shared based on the request from other researchers.
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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.
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 Combined With Chemotherapy in people with Esophageal Squamour Cell Cancer, run by Tianjin Medical University Cancer Institute and Hospital 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 1 inclusion and 1 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: opening soon, as of the sponsor's last update on 7 Feb 2025. 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 Hongjing Jiang, MD, PhD (022-23340123-6417, jianghongjing@tmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pathological complete response, pCR (time frame: From enrollment to the postoperative pathology report at 6 weeks). 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 7 Feb 2025.