Neoadjuvant Iruplinalkib and Bevacizumab in ALK-positive NSCLC: A Phase II Single-arm Trial

Laborértékek

• Hypersensitivity to iruplinalkib, bevacizumab, or any excipients.
  • Prior targeted therapy (TKI or mAb), immunotherapy, or investigational drugs for NSCLC.
  • Mixed small-cell and non-small-cell histology.
  • Other malignancy within 5 years, except cured basal cell carcinoma, early GI cancer (endoscopically resected), cervical CIS, DCIS, papillary thyroid cancer, or other cured cancers deemed not to affect survival.
  • Unstable systemic disease: active infection, uncontrolled hypertension (>160/110 mmHg), unstable angina or angina within 3 months, CHF (NYHA ≥II), MI within 6 months, clinically significant arrhythmia requiring treatment, or QTc >480 ms (average of 3 consecutive measurements if prolonged).
  • History of extensive diffuse interstitial lung disease or grade 3/4 pulmonary fibrosis/ILD (excluding localized radiation pneumonitis).
  • Congenital or acquired immunodeficiency (e.g., HIV).
  • Major surgery within 4 weeks before study treatment, or planned major surgery during study.
  • Inability to swallow tablets or malabsorption affecting GI absorption.
  • Known risk of GI perforation or intestinal obstruction.
  • Pregnant or lactating women.
  • Any other condition (e.g., alcohol/drug abuse, serious concomitant disease including psychiatric, severe laboratory abnormalities, or social factors) that, in the investigator's opinion, could interfere with study conduct or patient safety.
  • History of abdominal fistula, GI perforation, intra-abdominal abscess, or thrombotic disease within 6 months, or judged intolerant to bevacizumab.
  • Evidence of hereditary bleeding diathesis or coagulopathy.
  • Minor surgery (e.g., catheter placement) within 48 hours before first bevacizumab infusion.
  • Imaging evidence of tumor invasion of major vessels (e.g., pulmonary artery or SVC) with bleeding risk per investigator.
  • Other factors making the patient unsuitable for the study per investigator.

• Signed informed consent.
  • Age 18-80 years, both sexes.
  • Histologically or cytologically confirmed NSCLC.
  • Stage II-III NSCLC per investigator, and ALK-positive.
  • At least one measurable lesion per RECIST 1.1.
  • ECOG performance status 0-1.
  • Adequate organ and bone marrow function (within 7 days before first dose, no transfusion or growth factor support within 14 days):
  • Hb ≥90 g/L, ANC ≥1.5×10⁹/L, PLT ≥90×10⁹/L;
  • Cr ≤1.5×ULN; TBIL ≤1.5×ULN; ALT/AST ≤3.0×ULN (or ≤5.0×ULN if liver metastases), ALB ≥25 g/L;
  • INR ≤1.5×ULN, PT/APTT ≤1.5×ULN (or within therapeutic range for anticoagulated patients).
  • FEV₁ >60% predicted.
  • Women of childbearing potential: negative pregnancy test (serum/urine) within 7 days before enrollment and use of reliable contraception from screening to 3 months after last study drug. Men: adequate contraception or surgically sterile.
  • Expected survival ≥12 weeks.