Abstract 128TiP
Background
BRAF V600 mutations and MET exon 14 skipping (METex14) mutations are both recognized as actionable oncogenic drivers in NSCLC, respectively accounting for 1-2% of newly diagnosed cases. Metastatic NSCLC with BRAF V600 or METex14 mutations could be effectively treated with dabrafenib plus trametinib or capmatinib. For patients with non-metastatic, resectable diseases, surgery with neoadjuvant or adjuvant chemotherapy is the standard of care. Nevertheless, a significant proportion of patients still undergo disease recurrence after complete resection and (neo)adjuvant chemotherapy. In NSCLC with oncogenic EGFR or ALK alterations, targeted therapies in the adjuvant and neoadjuvant setting have demonstrated promising efficacy. While whether patients with BRAF V600 or METex14 mutations could benefit from neoadjuvant, and adjuvant targeted therapies remains unknown.
Trial design
This is a multi-center, phase II, two cohort study to evaluate the safety and efficacy of neoadjuvant and adjuvant targeted therapies in patients with BRAF V600- or METex14-positive NSCLC. Eligible patients are ≥ 18 years, diagnosed with stage IB-IIIA and selected IIIB (AJCC V8) NSCLC, have BRAF V600 or METex14 mutations, eligible for surgical resection and scheduled for surgery within 6 weeks after the last does of neoadjuvant treatment. Patients will receive neoadjuvant targeted therapy with dabrafenib plus trametinib or capmatinib for 8 weeks before surgery, followed by a two-year adjuvant targeted treatment. Other pre-surgical anticancer treatments are not allowed. The application of adjuvant chemotherapy for a maximal of 4 cycles is at the discretion of the treating physician. The two molecularly defined cohorts will be enrolled in parallel, with an estimated target enrollment of 20 patients for each. Primary endpoint is the complete pathologic response (pCR) rate based on local review. Secondary endpoints include major pathological response (MPR) rate, event-free survival (EFS), disease-free survival (DFS), overall survival (OS) and safety.
Clinical trial identification
NCT06054191.
Legal entity responsible for the study
The authors.
Funding
Novartis.
Disclosure
All authors have declared no conflicts of interest.