Becotatug Vedotin Plus Tislelizumab and Low-Dose Lenvatinib for Advanced Esophageal Squamous Cell Carcinoma, Phase II

Korábbi kezelés

• Evidence of active infection, including:1）Hepatitis B (HBsAg positive with HBV DNA ≥ 2000 IU/mL, excluding drug-induced or other causes of hepatitis);2）Hepatitis C (anti-HCV antibody positive with HCV RNA above the lower limit of detection);3）Human immunodeficiency virus (HIV) infection;4）Uncontrolled active bacterial, viral, fungal, rickettsial, or parasitic infections that have not resolved prior to study drug administration.
• Third-space fluid that cannot be controlled by drainage (e.g., massive ascites, pleural effusion, pericardial effusion), or subjects requiring drainage to control third-space fluid within 14 days prior to first dose.
• Intravenous antibiotic therapy within 7 days prior to first dose.
• Investigational drug from another clinical trial within 4 weeks prior to first dose.
• Live attenuated vaccine within 4 weeks prior to first dose. Inactivated seasonal influenza vaccines or approved non-replicating COVID-19 vaccines are permitted.
• Systemic immunostimulatory agents (including but not limited to interferon, interleukin-2, etc.) within 4 weeks prior to first dose.
• Major surgical procedure (e.g., abdominal or thoracic surgery, excluding diagnostic puncture, infusion device placement, or gastrointestinal stent placement) within 4 weeks prior to first dose, or anticipation of major surgery not directed at the tumor during the study treatment period.
  • 15.History of substance abuse (psychoactive drugs) that cannot be abstained from, or psychiatric disorders.
  • 16.Concurrent participation in another interventional clinical study. 17.Any other condition that, in the investigator's judgment, makes the subject unsuitable for participation in this clinical trial.

Más betegség

• Prior malignancy within 5 years, except for carcinoma in situ, basal cell carcinoma, or other malignancies considered cured with negligible risk of recurrence.
• Known hypersensitivity to any component of the study regimen.
• High risk of gastrointestinal bleeding, esophageal fistula, or esophageal perforation.
• Untreated or unstable parenchymal brain metastases, spinal cord metastasis or compression, leptomeningeal disease, or meningeal metastases.
• Any severe or uncontrolled systemic disease in the investigator's judgment.

Laborértékek

• Poorly controlled cardiac disease, including:
  • 1）Heart failure > New York Heart Association (NYHA) class II; 2）Unstable angina pectoris; 3）Myocardial infarction within 1 year; 4）Clinically significant supraventricular or ventricular arrhythmias requiring treatment; 5）Long QT syndrome, with QTcF > 450 ms (male) or QTcF > 470 ms (female). 9.History of primary immunodeficiency or active autoimmune disease, or current use of immunosuppressants or systemic corticosteroids (≥ 10 mg/day prednisone or equivalent) continuing within 2 weeks prior to enrollment.
  • 10.History of or concomitant interstitial lung disease (ILD), radiation pneumonitis, severe chronic obstructive pulmonary disease (COPD), severe pulmonary insufficiency, or symptomatic bronchospasm.
  • 11.Positive serum pregnancy test or breastfeeding females who do not agree to use adequate contraception during the study and for 6 months after the last dose of study drug.
  • 12.History of organ transplantation, including allogeneic peripheral stem cell or bone marrow transplantation.
  • 13.Peripheral neuropathy ≥ Grade 2 (per CTCAE version 5.0). 14.Prior receipt of any of the following treatments:

• 1.Age ≥ 18 years, male or female. 2.Histopathologically or cytologically confirmed recurrent or metastatic esophageal squamous cell carcinoma.
• 3.Failed first-line or above standard systemic therapy for advanced disease. 4.Patients must be able to provide tumor specimens (paraffin blocks, paraffin-embedded sections, or fresh tissue sections) from primary or metastatic lesions for pathological testing. The most recent archived tumor tissue specimen may be used. If archived tissue is unavailable, a new biopsy is required.
• 5.ECOG PS 0-2. 6.Expected survival ≥ 3 months. 7.At least one measurable target lesion assessable by CT or MRI according to RECIST version 1.1 criteria.
• 8.Adequate organ and bone marrow function, as demonstrated by the following laboratory values:
• Bone marrow: Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L；Platelet count (PLT) ≥ 100×10⁹/L；Hemoglobin (HGB)≥90 g/L.
• Liver: Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤2.5×ULN; for patients with liver metastases, ALT and AST≤5×ULN.
• Kidney: Creatinine clearance (Ccr) ≥ 50 mL/min (calculated using the Cockcroft-Gault formula).
• Coagulation: International normalized ratio (INR) ≤ 1.5 × ULN and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (except for patients receiving therapeutic anticoagulation).
• Cardiac function: No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥ 50%.
  • 9.Female patients of childbearing potential must agree to use contraception during the study and for 6 months after the end of study participation, have a negative serum or urine pregnancy test within 7 days prior to study enrollment, and must not be breastfeeding. Male patients must agree to use contraception during the study and for 6 months after the end of study participation.
  • 10.Patients must be able and willing to comply with the scheduled visits, treatment plans, laboratory tests, and other study-related procedures as outlined in the protocol.
  • 11.Patients must be able to understand the study and voluntarily sign the informed consent form.