Histologically confirmed recurrent or metastatic or unresectable locally advanced ESCC
Conditions
Interventions
Single arm:Low-Dose Radiotherapy Sequential with Sacituzumab Tirumotecan and Bemozumab
Sponsors
Zhejiang Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Histopathologically confirmed unresectable, locally advanced or metastatic esophageal squamous cell carcinoma. 2. Positive TROP2 expression (IHC>=1+). 3. Have progressed on or are intolerant to one prior first-line standard regimen of chemotherapy combined with immunotherapy (containing PD-1 or PD-L1 inhibitors), and are planning to receive second-line therapy. 4. Able to provide written voluntary informed consent, and willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other requirements of the study. 5. Both male and female, aged 18 to 75 years (inclusive). 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and life expectancy>=3 months. 7. Presence of measurable lesions per RECIST 1.1 criteria: long diameter>=10 mm for non-nodal lesions, and short diameter>=15 mm for malignant nodal lesions. 8. Adequate organ and bone marrow function (without receiving blood transfusion, recombinant human thrombopoietin, or colony-stimulating factor therapy within 2 weeks prior to the first dose): (1). Hematology: Absolute neutrophil count (NEUT#)>=1.2×10^9/L; Platelets (PLT) >=100×10^9/L; Hemoglobin>=9 g/dL. (2). Liver function: Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) =3 g/dL. (3). Renal function: Creatinine clearance>=50 mL/min (calculated using the Cockcroft-Gault formula). 9. Subjects must have recovered from all acute toxicities due to prior therapy to Grade 1, with the exception of alopecia and vitiligo. Note: Subjects with endocrine adverse events of any grade who are stable and asymptomatic with appropriate hormone replacement therapy only are permitted for enrollment. 10. Female patients of childbearing potential and male patients with partners of childbearing potential must agree to use highly effective contraceptive methods during the study treatment period. Female and male patients receiving SKB264 should continue contraception for 6 months after the last dose.
Exclusion criteria
Exclusion criteria: 1. Recent anti tumor therapy: Received anti tumor treatment other than the first line standard chemotherapy combined with immunotherapy within 2 weeks prior to the first dose of study intervention. 2. Esophageal stent or interventional procedure: Received esophageal stent placement or interventional surgery (e.g., for bleeding) within 2 weeks prior to the first dose of study intervention. 3. Esophageal complications: Presence of esophageal perforation, esophageal leakage, or active bleeding from the primary esophageal lesion. 4. Effusions: Pleural, peritoneal, or pericardial effusion requiring drainage or diuretic therapy within 2 weeks prior to the first dose of study intervention. 5. Prior TROP 2 targeted ADC therapy: Prior treatment with an antibody drug conjugate (ADC) targeting trophoblast cell surface antigen 2 (TROP 2). 6. Severe ocular disease: History of severe dry eye syndrome, severe meibomian gland disease, and/or blepharitis, or corneal disease that affects or delays corneal healing. 7. Active brain metastases or peripheral neuropathy: Active brain metastases or peripheral neuropathy = Grade 2. 8. Inflammatory bowel disease: Active inflammatory bowel disease requiring immunosuppressive medication, or a history of inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis, or chronic diarrhea). 9. Cardiovascular disease: Uncontrolled major cardiovascular or cerebrovascular disease, including New York Heart Association (NYHA) Class III or IV heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, corrected QT interval (QTcF) prolonged to >480 ms, and/or other serious cardiovascular and cerebrovascular diseases within 6 months prior to the first dose of study intervention. 10. Vaccination: Received live or live attenuated vaccine within 30 days prior to the first dose of study intervention. 11. CYP3A4 inducers/inhibitors: Currently using strong and/or moderate inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued throughout the study intervention period. A washout period of 2 weeks is required before starting the study intervention. 12. Investigational drug or device: Received an investigational drug or used an investigational device within 4 weeks prior to the first dose of study intervention. 13. Other malignancies: Known other malignancies that are progressing or have required active treatment within the past 3 years. 14. CNS metastases or carcinomatous meningitis: Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. 15. Active infection: Active infection requiring systemic therapy. 16. HIV related disease: History of Kaposi’s sarcoma and/or multicentric Castleman’s disease in HIV infected patients. 17. Hepatitis B and C co infection: Concurrent active hepatitis B (defined as hepatitis B surface antigen [HBsAg] positive and/or detectable hepatitis B virus [HBV] DNA) and hepatitis C virus infection (defined as hepatitis C virus antibody [Ab] positive and detectable hepatitis C virus RNA). 18. Recent major surgery or trauma: Received major surgery or severe traumatic injury within 4 weeks prior to the first dose of study intervention. Planned major surgery during the study intervention period is also an exclusion criterion. 19. Severe allergic reaction: History of severe allergic reaction (= Grade 3) to SKB264, any of its excipients, and/or another biologic therapeutic agent. 20. Interstitial lung di
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ORR (Objective Response Rate); | — |
Secondary
| Measure | Time frame |
|---|---|
| Occurrence of adverse events (AEs);Disease Control Rate;Duration of Response;median Progression-Free Survival;median Overall Survival; | — |
Countries
China
Contacts
Public ContactYongling Ji
Zhejiang Cancer Hospital
Outcome results
None listed