Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor worldwide, with particularly high incidence in East Asian regions such as China, and is associated with poor patient prognosis. In recent years, immune checkpoint inhibitors (e.g., anti-PD-1/PD-L1 antibodies) combined with chemotherapy have become the standard first-line treatment for advanced ESCC. Multiple randomized controlled trials have confirmed that this combination significantly improves patient survival compared to chemotherapy alone. However, a subset of patients still exhibit poor response or develop resistance to the immunotherapy-chemotherapy regimen, necessitating the exploration of novel combination strategies to further enhance efficacy.
The epidermal growth factor receptor (EGFR) is frequently overexpressed in ESCC and is associated with tumor proliferation, metastasis, and poor prognosis, making it an important therapeutic target. Antibody-drug conjugates (ADCs) targeting EGFR achieve precise tumor killing by conjugating an anti-EGFR antibody to a potent cytotoxic payload. Preclinical studies have demonstrated significant antitumor activity of EGFR ADCs in ESCC models. Mechanistically, anti-EGFR therapy and immune checkpoint inhibitor therapy may exert synergistic effects through several avenues: enhancing tumor antigen presentation, remodeling the tumor microenvironment, and modulating PD-L1 expression. Therefore, this triple combination strategy holds promise for overcoming the limitations of monotherapies and providing a new treatment option for patients with ESCC.
Age ≥ 18 years.
Male or non-pregnant, non-lactating female.
ECOG performance status of 0 or 1, with no deterioration within 7 days.
Histologically confirmed locally advanced or metastatic esophageal squamous cell carcinoma.
Prior treatment with any anti-EGFR monoclonal antibody, or with anti-PD-1/PD-L1 antibody, anti-PD-L2 antibody, anti-CD137 antibody, CTLA-4 antibody, or any other drug/antibody targeting T-cell co-stimulation or checkpoint pathways.
Administration of a live vaccine within 4 weeks prior to enrollment or anticipated during the study period.
Active autoimmune disease or a history of autoimmune disease within 4 weeks prior to enrollment.
Prior allogeneic bone marrow transplantation or solid organ transplant.