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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
104
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.
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.
Fudan University Shanghai Cancer Center
Shanghai, China
RECRUITINGObjective 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)
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)
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
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.
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