Vebrekotuzumab ± Anti-PD-1 in Pretreated Advanced ESCC

Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorFudan University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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+).

Disqualifiers

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.

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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.

  • 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.

Treatment groups

104 Participants
are divided into 2 treatment groups
Group A: Vebrekotuzumab+PD-1Experimental treatment 2 interventions
Group B: VebrekotuzumabExperimental treatment 1 intervention

Trial outcomes

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.

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

Secondary outcomes

1

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.

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

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.

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
3

Overall survival (OS)

OS is defined as the time from the first dose of study treatment until death from any cause.

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

Other outcomes

Sponsors and contacts

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