neoadjuvant and adjuvant targeted treatment in nsclc with braf v600 or met exon 14 mutations

Conditions: NSCLC; BRAF V600 Mutation; MET Exon 14 Mutation

Summary: 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).

Eligibility criteria:
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.