Vebrekotuzumab ± Anti-PD-1 in Pretreated Advanced ESCC

NCT07403136 | Recruiting Phase 2 DMC

• 1 other identifier: ESO-Shanghai29
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief 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 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

Keywords

Esophageal Squamous Cell Carcinoma; Antibody-drug conjugate; Second-line

Outcome Measures

Primary Outcomes (1)

• 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.

  At the end of every 2 cycles (each cycle is 21 days)

Secondary Outcomes (3)

• Disease Control Rate (DCR)

  At the end of every 2 cycles (each cycle is 21 days)

• Progression-Free Survival (PFS)

  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)

  The time from the first dose of study treatment until death from any cause, assessed up to 24 months.

Study Arms (2)

Vebrekotuzumab+PD-1

EXPERIMENTAL

Vebrekotuzumab in combination with an immune checkpoint inhibitor.

Drug: Vebrekotuzumab; Drug: PD-1 antibody

Vebrekotuzumab

EXPERIMENTAL

Vebrekotuzumab monotherapy.

Drug: Vebrekotuzumab

Interventions

Vebrekotuzumab DRUG

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.

Vebrekotuzumab; Vebrekotuzumab+PD-1

PD-1 antibody DRUG

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.

Vebrekotuzumab+PD-1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

RECRUITING

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

spartalizumab

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

Central Study Contacts

Kuaile Zhao, M.D.

CONTACT

+86-18017312534; kuaile_z@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: January 5, 2026
• First Posted: February 11, 2026
• Study Start: April 30, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): January 31, 2029
• Last Updated: May 11, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)