Effective later-line treatment options remain an unmet medical need for patients with advanced esophageal squamous cell carcinoma (ESCC) whose disease has progressed after prior immunotherapy, particularly given the widespread use of immunotherapy in the first-line setting. This study is designed to evaluate the efficacy and safety of PD-1/IL-2α-bias bispecific antibody fusion protein monotherapy in patients with advanced or metastatic ESCC after failure of prior immune checkpoint inhibitor (ICI) plus platinum-based chemotherapy.

Inclusion Criteria:

1. Histologically or cytologically confirmed unresectable locally advanced or metastatic esophageal squamous cell carcinoma (ESCC)
2. Disease progression or treatment failure after prior immune checkpoint inhibitor (ICI) plus platinum-based chemotherapy
3. At least one measurable lesion according to RECIST version 1.1;
4. ECOG PS 0 to 1;
5. Age 18 to 75 years
6. 6.Life expectancy of ≥12 weeks.
7. Signed informed consent prior to study entry and willingness/ability to comply with study treatment, visits, and other protocol-specified procedures
8. Adequate organ function
9. Women of childbearing potential, or male patients whose sexual partners are women of childbearing potential, must use effective contraception throughout the treatment period and for 180 days after the last dose of study drug.

Exclusion Criteria:

1. Histology showing mixed squamous cell carcinoma, including but not limited to adenosquamous carcinoma, squamous cell carcinoma with small cell carcinoma components, carcinosarcoma, or sarcomatoid carcinoma.
2. Concurrent participation in another interventional clinical study, except for observational (non-interventional) studies or the follow-up phase of an interventional study.
3. Has received any treatment that is explicitly prohibited by the protocol.
4. Subjects with unresolved > Grade 1 toxicity associated with any prior antineoplastic therapy, with the exception of persistent Grade 2 alopecia, anemia, peripheral neuropathy, correctable electrolyte abnormalities, or stable endocrine abnormalities controlled with hormone replacement therapy.
5. Prior immune checkpoint inhibitor therapy permanently discontinued due to severe immune-related toxicity.
6. Clinically significant physical examination findings or laboratory abnormalities that, in the investigator's judgment, may interfere with study results or increase the risk of treatment-related complications.
7. Women who are pregnant or lactating
8. Active autoimmune disease or history of autoimmune disease
9. Known positive HIV test, active hepatitis B, hepatitis C (HCV), tuberculosis, or a history of these infections.
10. Clinically significant cardiovascular or cerebrovascular disease.
11. History of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring corticosteroid therapy, or any clinically evident active interstitial lung disease; idiopathic pulmonary fibrosis identified on baseline CT scan; or uncontrolled massive pleural effusion or pericardial effusion.
12. Uncontrolled or unstable intercurrent illness
13. For subjects with uncontrolled epilepsy, central nervous system disease, or mental illness, the investigator should assess whether such conditions may impair the subject's ability to provide informed consent or comply with the study protocol.
14. Poor gastrointestinal function, malabsorption syndrome, or active gastrointestinal ulcer.
15. History of organ transplantation or allogeneic hematopoietic stem cell transplantation.
16. Congenital or acquired immunodeficiency.
17. Severe malnutrition requiring parenteral nutrition support, except for malnutrition corrected for more than 4 weeks before the first dose of study treatment.
18. Uncontrolled metabolic disorder or other non-malignant organic/systemic disease or secondary effect of cancer that may result in high medical risk and/or uncertainty in survival assessment.
19. Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh class B or higher cirrhosis.
20. History of intestinal obstruction, inflammatory bowel disease, extensive bowel resection (partial colectomy or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis, chronic diarrhea, or any other acute/chronic disease, psychiatric disorder, or laboratory abnormality that may increase study risk, interfere with interpretation of results, or, in the investigator's judgment, make the patient unsuitable for study participation.
21. Another pathologically confirmed malignancy diagnosed within 5 years before the first dose, except for curatively treated basal-cell carcinoma of the skin, squamous-cell carcinoma of the skin, and/or carcinoma in situ after curative resection, localized prostate cancer after radical treatment, papillary thyroid carcinoma, and other malignancies that have been curatively treated, have had no known active disease for at least 2 years before study entry, and have an extremely low risk of recurrence.
22. Interstitial pneumonitis, pulmonary fibrosis, pneumoconiosis, drug-related pneumonitis, radiation pneumonitis, or other pulmonary conditions requiring corticosteroids or other treatment; history of severely impaired pulmonary function or other forms of restrictive lung disease.