Inclusion Criteria:
- Patients must meet all of the following inclusion criteria to participate in this study:
- Signed informed consent.
- Age ≥ 18 years.
- Histologically or cytologically confirmed NSCLC adenocarcinoma, with -postoperative pathology confirming stage IIA-IIIC.
- Willing to undergo curative resection, and assessed by a surgeon as operable with no surgical contraindications.
- No prior systemic anti-tumor therapy.
- Expected survival ≥ 6 months.
- At least one measurable or evaluable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2.
- MET alteration confirmed by NGS gene testing, including the following types:
MET exon 14 skipping mutation (NGS results from tissue or blood sample certified by CLIA or CAP).
- MET primary amplification, NGS positive or FISH GCN ≥6 (results from tissue or blood sample certified by CLIA or CAP or FISH assay).
- MET protein overexpression, immunohistochemistry showing ≥50% tumor cells with ++ or higher staining.
- Adequate pulmonary function to tolerate surgery.
- Adequate organ and bone marrow function, defined as:
- Hematology: absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; platelets ≥ 100 × 10⁹/L; hemoglobin ≥ 9.0 g/dL.
- Hepatic function: total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); for patients with HCC, liver metastases, or history/suspected Gilbert syndrome (persistent or recurrent hyperbilirubinemia, mainly unconjugated, without evidence of hemolysis or liver lesions), TBIL ≤ 3 × ULN; for patients without HCC or liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN.
- Renal function: serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance (CCr) ≥ 50 mL/min; urine dipstick protein < 2+.
- Coagulation: activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤ 1.5 × ULN.
Thyroid function: normal thyroid-stimulating hormone (TSH); if baseline TSH is outside the normal range, enrollment is allowed if total T3 (or FT3) and FT4 are within normal limits.
- Cardiac enzymes: within normal range (isolated laboratory abnormalities deemed clinically insignificant by the investigator are acceptable).
- Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to the first dose of study drug (Cycle 1, Day 1). If urine pregnancy test cannot be confirmed negative, a serum pregnancy test is required. Non-childbearing females are defined as postmenopausal for at least 1 year, or surgically sterile (bilateral oophorectomy or hysterectomy).
All subjects with potential risk of pregnancy (male or female) must use highly effective contraception with a failure rate <1% during treatment and for 120 days after the last dose of study drug (or 180 days after the last dose of chemotherapy).
Exclusion Criteria:
- Patients meeting any of the following criteria are not eligible for this study:
Presence of EGFR, ALK, ROS1, or other actionable mutations excluding MET. Receipt of live attenuated vaccines within 4 weeks prior to enrollment or planned during the study period.
- All participants must undergo brain imaging (MRI or contrast-enhanced CT) prior to enrollment to rule out brain metastases.
- Major surgery (e.g., thoracic, abdominal, or pelvic) within 4 weeks prior to study treatment initiation, or ongoing recovery from surgical complications.
Diagnosis of any malignancy other than NSCLC within 5 years prior to study treatment initiation (excluding completely resected basal cell carcinoma or squamous cell carcinoma of the skin, in situ carcinoma, or completely resected papillary thyroid carcinoma).
- Active, known, or suspected autoimmune disease.
- Known history of primary immunodeficiency.
- Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
- Known hypersensitivity to the study drug bozitinib, platinum-based doublet chemotherapy, or any excipients.
- Not fully recovered from any toxicity and/or complications caused by prior interventions (i.e., ≤ Grade 1 or returned to baseline, excluding fatigue or alopecia) prior to study treatment.
- Untreated active hepatitis B infection (defined as HBsAg positive with detectable HBV-DNA above the upper limit of normal at the local laboratory).
Note: Patients with hepatitis B meeting the following criteria may be enrolled:
HBV viral load <1000 copies/mL (200 IU/mL) prior to first dose; patients must receive antiviral therapy throughout chemotherapy to prevent viral reactivation.
Patients who are anti-HBc (+), HBsAg (-), anti-HBs (-), and HBV viral load (-) do not require prophylactic antiviral therapy but must be closely monitored for viral reactivation.
- Active hepatitis C infection (HCV antibody positive and HCV-RNA above the assay lower limit of detection).
- Any history, condition, treatment, or laboratory abnormality that could interfere with study results, hinder full participation, or that the investigator considers a potential risk or inappropriate for enrollment.