A Multicenter Phase II Randomized Trial of Limertinib Followed by Sintilimab and Chemotherapy vs. Limertinib Followed by Limertinib and Chemotherapy as Neoadjuvant Therapy in Resectable Stage II-IIIB EGFR-Mutant NSCLC

Korábbi kezelés

• Patients with stage I or IV NSCLC who have previously received systemic anti-tumor therapies (e.g., ICIs, targeted therapy, chemotherapy).
• Contraindications to local therapies (surgery, radiotherapy, or intervention) per investigator judgment.

Más betegség

• Active known or suspected autoimmune diseases (exceptions: type I diabetes, hypothyroidism requiring hormone replacement only, non-progressive skin conditions like vitiligo/psoriasis/alopecia).
• Active hepatitis B (HBsAg-positive) or hepatitis C (HCV RNA-positive). Patients with resolved HBV infection (HBsAg-negative, HBcAb-positive) must provide HBV DNA-negative results. HCV antibody-positive patients require negative HCV RNA PCR.
• HIV-positive or AIDS history.
• Arterial thrombosis within 6 months, or deep vein thrombosis/pulmonary embolism within 3 months.
• Uncontrolled angina, arrhythmias, or congestive heart failure.
• Active malignancies within 5 years (except cured cervical/cutaneous carcinoma in situ, superficial bladder/prostate/breast cancer).
• Hypersensitivity to sintilimab, limertinib, chemotherapy agents, or excipients.
• Any condition compromising trial integrity or patient safety, as judged by the investigator.

Egyéb

• Unwillingness to sign informed consent or comply with follow-up.

• Signed written informed consent form
• Age: 18-75 years.
• Cytologically/histologically confirmed (via percutaneous lung puncture, bronchoscopy, mediastinoscopy, etc.), previously untreated stage II-IIIB (IASLC 8th Edition Thoracic Tumor Classification) lung adenocarcinoma.
• Tumor tissue or blood samples confirmed as EGFR-sensitive or rare mutation-positive by laboratory testing
• Must provide archived tumor tissue or newly resected tumor biopsy samples for PD-L1 IHC testing during screening.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
• Measurable lesions per RECIST v1.1.
• Surgically evaluated as eligible for local surgical resection (adequate pulmonary/organ function).Surgically evaluated as eligible for local surgical resection (adequate pulmonary/organ function).
• Adequate organ and bone marrow function (within 7 days prior to enrollment; no corrective therapies within 14 days prior to testing): • Hematology: ANC ≥1.5×10⁹/L, platelets ≥100×10⁹/L, hemoglobin ≥100 g/L. • Hepatic: Total bilirubin ≤1.5×ULN; AST/ALT ≤2.5×ULN; albumin ≥35 g/L. • Renal: Serum creatinine ≤1.5×ULN; CrCl ≥60 mL/min (Cockcroft-Gault formula); urine protein <2+ or 24-hour urine protein <1 g. Cockcroft-Gault formula: • Female: CrCl = [(140 - age) × weight (kg) × 0.85] / [72 × serum creatinine (mg/dL)]. • Male: CrCl = [(140 - age) × weight (kg)] / [72 × serum creatinine (mg/dL)]. • Coagulation: INR ≤1.5×ULN; PT/APTT ≤1.5×ULN.
• For women of childbearing potential: Negative urine/serum pregnancy test within 7 days prior to first dose. Confirmatory blood test required if urine test is positive.