Esophageal Squamous Cell CarcinomaPhase 2NCT07403136
Becotatug Vedotin ± Anti-PD-1 in Pretreated Advanced ESCC
A Phase 2 study testing Vebrekotuzumab and PD-1 antibody in people with Esophageal Squamous Cell Carcinoma, run by Fudan University at 1 site in China.
Trial summary
This study will test a new potential treatment for advanced esophageal squamous cell cancer (ESCC) for patients whose initial treatment has stopped working. Currently, the standard second-line treatment for this cancer is PD-1 inhibitors or chemotherapy alone, which is not very effective, allowing the cancer to grow… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophageal Squamous Cell Carcinoma
- What is being tested?
- Vebrekotuzumab and PD-1 antibody
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 104 participants
- Where
- 1 siteChina
- Study dates
- 30 Apr 2026to 31 Jan 2029
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing to voluntarily sign the informed consent form and comply with the protocol requirements.
- Age ≥18 years on the day of signing the informed consent form, regardless of gender.
- Life expectancy ≥12 weeks.
- Patients with histologically confirmed advanced recurrent or metastatic esophageal squamous cell carcinoma (ESCC) and immunohistochemistry (IHC) confirmed positive epidermal growth factor receptor (EGFR) expression (IHC 1+, 2+, or 3+).
- Have experienced disease progression or intolerability after receiving at least one prior line of systemic therapy, which must have included an immune checkpoint inhibitor (e.g., anti-PD-1/PD-L1 antibody).
- The patient must be able to provide a tumor tissue sample (paraffin block, paraffin-embedded sections, or fresh tissue sections) from the primary or metastatic site for pathological testing. Archived tumor tissue from the most recent treatment should be used. If archived tissue is unavailable, a new biopsy must be performed.
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- Must have radiographic evidence of disease progression confirmed by the investigator during or after the last treatment regimen. At baseline, there must be at least one measurable extracranial lesion per RECIST 1.1 criteria (longest diameter ≥10 mm on CT scan, or for lymph nodes, short axis ≥15 mm). The measurable lesion should not have been previously irradiated, unless it is within a prior radiation field or was previously treated locally and has documented progression.
- All adverse events (AEs) from prior anti-tumor therapy have resolved to ≤ Grade 1 per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 (except for alopecia, non-clinically significant or asymptomatic laboratory abnormalities).
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to the first dose.
- No serious cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥50% confirmed by echocardiography or MUGA scan within 28 days prior to the first dose.
- Adequate organ function within 7 days prior to the first dose, as defined by:
- Bone marrow: Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L; platelet count ≥100 × 10⁹/L; hemoglobin ≥90 g/L. Patient must not have received any blood transfusion or blood component therapy within 14 days prior to the first dose, nor any biologic response modifiers (e.g., G-CSF, erythropoietin) within 7 days prior to the first dose.
- Liver: For patients without liver metastases: total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN. For patients with liver metastases: TBIL ≤1.5 × ULN; ALT and AST ≤5 × ULN.
- Kidney: Serum creatinine (Cr) ≤1.5 × ULN, or calculated creatinine clearance (Cockcroft-Gault formula) ≥50 mL/min.
- Coagulation: International normalized ratio (INR) ≤1.5 × ULN and activated partial thromboplastin time (aPTT) ≤1.5 × ULN (unless the patient is receiving therapeutic anticoagulation).
- Male patients with reproductive potential and female patients of childbearing potential must be willing to use effective contraception from signing the ICF until 6 months after the last dose of the study drug. Women of childbearing potential include premenopausal women and women within 2 years of menopause onset. A negative serum pregnancy test result must be confirmed for women of childbearing potential within ≤7 days prior to the first study drug dose.
Who cannot join
- History of other primary malignancies. Note: Except for adequately treated basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix; or patients with other malignancies who have undergone curative treatment and have been disease-free for ≥5 years may be enrolled.
- Untreated or unstable parenchymal brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease.
- Note: Patients who have received local therapy for brain metastases may be enrolled if brain imaging shows stability for at least 28 days prior to the first dose, with no evidence of cerebral edema, and no requirement for corticosteroid therapy.
- Presence of uncontrolled third-space fluid (e.g., significant ascites, pleural effusion, or pericardial effusion) that cannot be managed by drainage or other methods. Patients who required drainage to control third-space fluid within 14 days prior to the first dose are excluded.
- Any severe or uncontrolled systemic disease, in the investigator's judgment, including poorly controlled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg), poorly controlled diabetes mellitus, or active bleeding signs, etc.
- Poorly controlled cardiac disease, including heart failure of New York Heart Association (NYHA) class ≥II, unstable angina, myocardial infarction within the past year, clinically significant supraventricular or ventricular arrhythmia requiring treatment, or long QT syndrome, e.g., QTcF >450 ms (male) or QTcF >470 ms (female).
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- Evidence of active infection, including Hepatitis B (HBsAg positive AND HBV DNA ≥2000 IU/mL, excluding drug-induced or other causes of hepatitis), Hepatitis C (anti-HCV antibody positive AND HCV RNA above the lower limit of detection), or human immunodeficiency virus (HIV) infection; or uncontrolled active bacterial, viral, fungal, rickettsial, or parasitic infections, unless treated and resolved prior to study drug administration.
- History of hypersensitivity to any component of vebrekotuzumab (histidine, histidine hydrochloride, sucrose, mannitol, polysorbate 80) OR history of ≥Grade 3 hypersensitivity reactions to macromolecular protein agents/monoclonal antibodies.
- History of primary immunodeficiency or active autoimmune disease requiring systemic immunosuppressive therapy or systemic corticosteroid therapy (at doses ≥10 mg/day prednisone or equivalent) within 2 weeks prior to enrollment.
- Note: Patients with type I diabetes mellitus, hypothyroidism managed with stable hormone replacement therapy (including that caused by autoimmune thyroid disease), psoriasis not requiring systemic therapy, or vitiligo may be enrolled.
- History of or concurrent interstitial lung disease, radiation pneumonitis, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic bronchospasm, etc.
- Female patients who are pregnant (positive serum pregnancy test), breastfeeding, or unwilling to use adequate contraception during the study period and for 6 months after the last dose of study drug.
- Any other condition that, in the investigator's opinion, would make the patient unsuitable for participation in this clinical trial.
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
Fudan University Shanghai Cancer Center
Shanghai, 200032
Kuaile Zhao, M.D, 86-18017312534, kuaile_z@fudan.edu.cn
About this study
Official title: An Open-Label, Randomized Phase II Study of Becotatug Vedotin With or Without PD-1 Inhibitor Immunotherapy in Patients With Advanced Esophageal Squamous Cell Carcinoma Refractory to Previous Immunochemotherapy
This study will test a new potential treatment for advanced esophageal squamous cell cancer (ESCC) for patients whose initial treatment has stopped working. Currently, the standard second-line treatment for this cancer is PD-1 inhibitors or chemotherapy alone, which is not very effective, allowing the cancer to grow again after just 1.6 to 3.4 months on average. Therefore, there is a strong need for more effective therapies.
The new treatment is a type of drug called an antibody-drug conjugate (ADC). It is designed to target a specific protein called EGFR, which is found in high amounts on the surface of 50-70% of ESCC cancer cells and is linked to a poorer outlook for patients. This ADC works like a targeted delivery system: an antibody guides a powerful cell-killing drug directly to the cancer cells, aiming to destroy them while reducing harm to healthy cells. Although other drugs targeting EGFR have not successfully improved survival for ESCC patients, this new ADC offers a different and promising approach.
The main goal of this study is to find out if this new EGFR-targeting ADC is effective in helping patients with advanced ESCC live longer without their cancer getting worse.
- Conditions
- Esophageal Squamous Cell Carcinoma
- Being tested
- Vebrekotuzumab, PD-1 antibody
- Keywords
- Esophageal Squamous Cell Carcinoma, Antibody-drug conjugate, Second-line
- 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.
VebrekotuzumabDrug
This two-cohort study investigates the novel combination of vebrekotuzumab (an EGFR-targeting ADC) with a PD-1 inhibitor versus vebrekotuzumab monotherapy in patients with advanced ESCC refractory to first-line therapy. It uniquely provides a head-to-head comparison to evaluate the synergistic potential of combining targeted cytotoxicity with immune checkpoint blockade in this specific, treatment-resistant population.
PD-1 antibodyDrug
The PD-1 inhibitor (e.g., pembrolizumab) will be used exclusively in Cohort 1 in combination with vebrekotuzumab. This combination is designed to simultaneously deliver targeted cytotoxicity and immune checkpoint blockade, exploring their potential synergy in patients with advanced ESCC who have progressed after first-line therapy.
| Study group | Role | What they receive |
|---|---|---|
| Vebrekotuzumab+PD-1 | Experimental | Vebrekotuzumab in combination with an immune checkpoint inhibitor. Receives: Drug: Vebrekotuzumab; Drug: PD-1 antibody |
| Vebrekotuzumab | Experimental | Vebrekotuzumab monotherapy. Receives: Drug: Vebrekotuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
ORR is defined as the proportion of subjects in the trial who achieved a confirmed complete response (CR) or partial response (PR) as assessed by the investigator according to RECIST v1.1 and iRECIST criteria.
Measured: At the end of every 2 cycles (each cycle is 21 days)
Secondary outcomes (3)
Disease Control Rate (DCR)
DCR is defined as the proportion of subjects achieving complete response (CR), partial response (PR), or stable disease (SD) sustained for at least 5 weeks from the first dose, as assessed by the Independent Review Committee (IRC) per RECIST v1.1 and iRECIST criteria.
Measured: At the end of every 2 cycles (each cycle is 21 days)
Progression-Free Survival (PFS)
PFS is defined as the time from the first dose of study treatment until disease progression or death from any cause, whichever occurs first.
Measured: The time from the first dose of study treatment until disease progression or death from any cause, whichever occurs first, assessed up to 24 months
Overall survival (OS)
OS is defined as the time from the first dose of study treatment until death from any cause.
Measured: The time from the first dose of study treatment until death from any cause, assessed up to 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2026
- Study start30 Apr 2026
- Primary completion1 Aug 2027 (estimated)
- Study completion31 Jan 2029 (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 Fudan UniversityThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 104 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kuai Le Zhao, MD, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07403136
- Sponsor's protocol ID
- ESO-Shanghai29
- Status last verified
- May 2026
- First submitted
- 5 Jan 2026
- Last updated
- 7 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Randomized Phase II Study of Becotatug Vedotin With or Without PD-1 Inhibitor Immunotherapy in Patients With Advanced Esophageal Squamous Cell Carcinoma Refractory to Previous Immunochemotherapy
- ClinicalTrials.gov ID
- NCT07403136
- Acronym / sponsor ID
- ESO-Shanghai29
- Conditions
- Esophageal Squamous Cell Carcinoma
- Keywords
- Esophageal Squamous Cell Carcinoma, Antibody-drug conjugate, Second-line
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 104 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 30 Apr 2026 (actual)
- Primary completion
- 1 Aug 2027 (estimated)
- Study completion
- 31 Jan 2029 (estimated)
- First posted
- 11 Feb 2026 (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.
This study will test a new potential treatment for advanced esophageal squamous cell cancer (ESCC) for patients whose initial treatment has stopped working. Currently, the standard second-line treatment for this cancer is PD-1 inhibitors or chemotherapy alone, which is not very effective, allowing the cancer to grow again after just 1.6 to 3.4 months on average. Therefore, there is a strong need for more effective therapies.
The new treatment is a type of drug called an antibody-drug conjugate (ADC). It is designed to target a specific protein called EGFR, which is found in high amounts on the surface of 50-70% of ESCC cancer cells and is linked to a poorer outlook for patients. This ADC works like a targeted delivery system: an antibody guides a powerful cell-killing drug directly to the cancer cells, aiming to destroy them while reducing harm to healthy cells. Although other drugs targeting EGFR have not successfully improved survival for ESCC patients, this new ADC offers a different and promising approach.
The main goal of this study is to find out if this new EGFR-targeting ADC is effective in helping patients with advanced ESCC live longer without their cancer getting worse.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vebrekotuzumab+PD-1 | Experimental | Drug: Vebrekotuzumab, Drug: PD-1 antibodyVebrekotuzumab in combination with an immune checkpoint inhibitor. |
| Vebrekotuzumab | Experimental | Drug: VebrekotuzumabVebrekotuzumab monotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Willing to voluntarily sign the informed consent form and comply with the protocol requirements.
- Age ≥18 years on the day of signing the informed consent form, regardless of gender.
- Life expectancy ≥12 weeks.
- Patients with histologically confirmed advanced recurrent or metastatic esophageal squamous cell carcinoma (ESCC) and immunohistochemistry (IHC) confirmed positive epidermal growth factor receptor (EGFR) expression (IHC 1+, 2+, or 3+).
- Have experienced disease progression or intolerability after receiving at least one prior line of systemic therapy, which must have included an immune checkpoint inhibitor (e.g., anti-PD-1/PD-L1 antibody).
Key exclusion criteria (13 listed)
- History of other primary malignancies. Note: Except for adequately treated basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix; or patients with other malignancies who have undergone curative treatment and have been disease-free for ≥5 years may be enrolled.
- Untreated or unstable parenchymal brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease.
- Note: Patients who have received local therapy for brain metastases may be enrolled if brain imaging shows stability for at least 28 days prior to the first dose, with no evidence of cerebral edema, and no requirement for corticosteroid therapy.
- Presence of uncontrolled third-space fluid (e.g., significant ascites, pleural effusion, or pericardial effusion) that cannot be managed by drainage or other methods. Patients who required drainage to control third-space fluid within 14 days prior to the first dose are excluded.
- Any severe or uncontrolled systemic disease, in the investigator's judgment, including poorly controlled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg), poorly controlled diabetes mellitus, or active bleeding signs, etc.
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 |
|---|---|---|
| VebrekotuzumabThis two-cohort study investigates the novel combination of vebrekotuzumab (an EGFR-targeting ADC) with a PD-1 inhibitor versus vebrekotuzumab monotherapy in patients with advanced ESCC refractory to first-line therapy. It uniquely provides a head-to-head comparison to evaluate the synergistic potential of combining targeted cytotoxicity with immune checkpoint blockade in this specific, treatment-resistant population. | Drug | Vebrekotuzumab, Vebrekotuzumab+PD-1 |
| PD-1 antibodyThe PD-1 inhibitor (e.g., pembrolizumab) will be used exclusively in Cohort 1 in combination with vebrekotuzumab. This combination is designed to simultaneously deliver targeted cytotoxicity and immune checkpoint blockade, exploring their potential synergy in patients with advanced ESCC who have progressed after first-line therapy. | Drug | Vebrekotuzumab+PD-1 |
Primary outcome
Objective Response Rate (ORR)
Time frame: At the end of every 2 cycles (each cycle is 21 days)
ORR is defined as the proportion of subjects in the trial who achieved a confirmed complete response (CR) or partial response (PR) as assessed by the investigator according to RECIST v1.1 and iRECIST criteria.
3 secondary outcomes
Disease Control Rate (DCR)
Time frame: At the end of every 2 cycles (each cycle is 21 days)
Progression-Free Survival (PFS)
Time frame: The time from the first dose of study treatment until disease progression or death from any cause, whichever occurs first, assessed up to 24 months
Overall survival (OS)
Time frame: The time from the first dose of study treatment until death from any cause, assessed up to 24 months.
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 Jul 2026.
- Individual participant dataSharing planned: No
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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 Vebrekotuzumab and PD-1 antibody in people with Esophageal Squamous Cell Carcinoma, run by Fudan University 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 16 inclusion and 13 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 7 Jul 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 Kuaile Zhao, M.D. (+86-18017312534, kuaile_z@fudan.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: At the end of every 2 cycles (each cycle is 21 days)). 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 Jul 2026.