This is a Phase II, two parallel group study assessing the efficacy and safety of neoadjuvant and adjuvant targeted therapy in patients with stage IB-IIIA NSCLC harboring BRAF V600 or MET exon14 mutations.

This is a Phase II, two parallel group study assessing the efficacy and safety of neoadjuvant and adjuvant targeted therapy in patients with stage IB-IIIA NSCLC harboring BRAF V600 or MET exon14 mutations. Eligible patients with BRAF V600 mutations will receive dabrafenib 150mg bid plus trametinib 2mg qd for 8 weeks before a surgical resection (neoadjuvant), and followed by up to 4 cycles of adjuvant chemotherapy, if receive adjuvant chemotherapy, up to four cycles, chemo regimen according to investigators' choice, and up to 2 years of adjuvant targeted therapy with dabrafenib plus trametinib. For patients with MET exon14 mutations, they will receive capmatinib 400mg bid for 8 weeks before surgery (neoadjuvant), followed by up to 4 cycles of adjuvant chemotherapy, about adjuvant chemotherapy same as BRAF V600 group, and up to 2 years of adjuvant targeted therapy with capmatinib post-surgery. During treatment, patients will visit their physicians regularly for disease and safety assessment. After the end of treatment, survival follow-up will be conducted every 3 months for up to 3 years. Approximately 40 evaluable patients will be enrolled in the study (20 patients in each cohort).

Inclusion Criteria:

• 18 years or older.
• Histologically or cytologically diagnosed stage IB-IIIA and selected IIIB (T3N2, T4N2) NSCLC.
• Presence of BRAF V600 mutation or METex14 skip mutation in tumor (by PCR or NGS) or blood (by NGS) (pre-treatment biopsy confirmed) in local or other Clinical Laboratory Improvement Amendments (CLIA)-certified lab.
• Patients whose pre-surgical lesion is measurable, Eligible for surgical resection and scheduled for surgery within 2 weeks after the last does of neoadjuvant treatment.
• ECOG performance-status score of 0 or 1.
• No previous anticancer therapy.
• Patients with stage II or higher non-small-cell lung cancer (NSCLC) and those with suspected brain metastases should have brain imaging (CT or MRI) prior to enrollment to exclude brain metastasis.
• Could provide pretreatment tumor samples available for biomarker analysis. The subject should have good compliance, who would participate in the research voluntarily, and sign the informed consent.

Exclusion Criteria:

• Patients with unresectable (regardless of stage) or metastatic disease (stage IV) or brain metastases.
• Contain neuroendocrine carcinoma tumor histology.
• Major surgery within 4 weeks before enrollment, or who have not recovered from side effects of related procedures.
• History of current interstitial lung disease or pneumonitis.
• Patients with conditions requiring systemic corticosteroids (>10 mg daily prednisone or equivalent) or immunosuppressive medication within 14 days of the first dose of study drug (Inhaled or topical steroids and adrenal-replacement steroids are allowed).
• History of other malignancies within 5 years (excluding basal cell carcinoma of the skin or other carcinoma in situ that has been resected).
• Pregnant or lactating women.
• Those who are allergic to the research drug or its components.
• Subjects who are deemed unable to comply with the study requirements or complete the study.
• Those with acquired immunodeficiency syndrome, or any uncontrolled medical disorder, or insufficient function of bone marrow or other important organs.