Neoadjuvant Adebrelimab Plus Chemotherapy for Esophageal Cancer: A Clinical Study

Korábbi kezelés

• Poor nutritional status with a Body Mass Index <18.5 kg/m² (BMI <18.5 kg/m²); subjects whose BMI is corrected with targeted nutritional support prior to randomization may be considered for enrollment at the discretion of the principal investigator;
• Previous or ongoing receipt of any of the following therapies:
  • Any radiotherapy, chemotherapy, immunotherapy, targeted therapy, or other antitumor therapy for malignancy;
  • Systemic immunosuppressive therapy or systemic corticosteroid therapy for immunosuppressive purposes (prednisone >10 mg/day or equivalent dose) within 2 weeks prior to the first dose of study drug; Inhaled or topical steroids, and corticosteroid replacement therapy at prednisone >10 mg/day or equivalent dose are permitted in the absence of active autoimmune disease;
  • Live attenuated vaccine within 4 weeks prior to the first dose of study drug;
  • Major surgery or severe traumatic injury within 4 weeks prior to the first dose of study drug;
• Severe infection (Common Terminology Criteria for Adverse Events Grade >2 (CTCAE Grade >2)) within 4 weeks prior to the first dose of study drug, such as severe pneumonia requiring hospitalization, bacteremia, infectious complications, etc.
  • Subjects with active pulmonary inflammation on baseline chest imaging, signs/symptoms of infection, or requiring oral or intravenous antibiotic therapy within 14 days prior to the first dose of study drug are excluded, except for prophylactic antibiotic use;
• Active tuberculosis confirmed by medical history or CT scan, history of active tuberculosis within 1 year prior to enrollment, or history of active tuberculosis more than 1 year prior to enrollment without standard anti-tuberculosis treatment;
• Hereditary bleeding diathesis or coagulopathy. Clinically significant bleeding or documented bleeding tendency within 3 months prior to enrollment, including gastrointestinal bleeding, hemorrhagic gastric ulcer, and stool occult blood ≥++ at baseline;
• Diagnosis of another malignancy within 5 years prior to the first dose of study drug, except for malignancies with low metastatic or mortality risk (5-year survival rate >90%), such as adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix, which may be considered for enrollment;
• Any other conditions judged by the investigator that may result in premature study discontinuation, including concurrent treatment for other severe diseases (including psychiatric disorders), alcoholism, substance abuse, or family/social factors that may compromise subject safety or study compliance.

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• History of hypersensitivity to monoclonal antibodies, any component of adebrelimab, paclitaxel, cisplatin, or other platinum-based agents;
• Any active autoimmune disease or history of autoimmune disease, including but not limited to: interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism; subjects with hypothyroidism controlled by hormone replacement therapy may be considered for enrollment.
  • Subjects with fully resolved psoriasis or childhood asthma/allergies requiring no adult intervention may be considered, while those requiring medical intervention with bronchodilators are excluded;
• History of immunodeficiency, including positive HIV test, other acquired or congenital immunodeficiency disorders, history of organ transplantation, or allogeneic bone marrow transplantation;
• Poorly controlled cardiac symptoms or diseases, including but not limited to:
  • Heart failure of New York Heart Association Class II (NYHA Class II) or higher;
  • Unstable angina pectoris;
  • Myocardial infarction within 1 year;
  • Clinically significant supraventricular or ventricular arrhythmias that are either untreated or poorly controlled despite clinical intervention;

Egyéb

• Significant tumor invasion into adjacent organs of the esophageal lesion (e.g., major arteries or trachea);
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
• Female subjects who are pregnant or breastfeeding;

• Provided written informed consent and voluntarily enrolled in this study;
• Aged 18-75 years, male or female;
• Histologically or cytologically confirmed esophageal squamous cell carcinoma (ESCC);
• Clinical stage: cT1b-cT2N+M0 or cT3-cT4a any N M0;
• At least one measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) criteria: long axis ≥10 mm on spiral CT for target lesions, or short axis ≥15 mm for malignant lymph nodes;
• Predicted to be eligible for R0 resection;
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 (see Appendix 1);
• No prior anti-tumor therapy for esophageal cancer, including radiotherapy, chemotherapy, surgery, etc.;
• Planned to undergo surgical resection after completion of neoadjuvant therapy;
• No contraindications to surgery;
• Adequate organ function, as defined below:
  • Hematologic parameters (no blood products, colony-stimulating factors, leukocyte-raising agents, platelet-raising agents, or anti-anemia agents permitted within 14 days prior to the first dose of study drug):
  • White blood cell (WBC) count ≥ 3.0×10⁹/L Absolute neutrophil count (ANC) ≥ 1.0×10⁹/L Platelet count ≥ 80×10⁹/L Hemoglobin ≥ 90 g/L
  • Blood biochemistry:
  • Total bilirubin ≤ 1.5×ULN Alanine transaminase (ALT) ≤ 2.5×ULN; aspartate transaminase (AST) ≤ 2.5×ULN Serum creatinine ≤ 1.5×ULN, or creatinine clearance ≥ 50 mL/min (calculated by the Cockcroft-Gault formula, see Appendix 2)
  • Coagulation function:
  • International normalized ratio (INR) ≤ 1.5×ULN Activated partial thromboplastin time (APTT) ≤ 1.5×ULN
• Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 72 hours before initiation of study drug administration, and use effective contraception (e.g., intrauterine device, oral contraceptives, condoms) during the trial and for at least 3 months after the last dose.Male subjects with female partners of childbearing potential must use effective contraception during the trial and for 3 months after the last dose;
• Good subject compliance and willingness to comply with study follow-up requirements.