A Phase II, Two Parallel Group Study of Neoadjuvant and Adjuvant Targeted Treatment in NSCLC With BRAF V600 or MET Exon 14 Mutations
Overview
- Phase
- Phase 2
- Intervention
- Dabrafenib + Trametinib
- Conditions
- NSCLC
- Sponsor
- Sun Yat-sen University
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Pathological complete response (pCR) rate
- Status
- Not yet recruiting
- Last Updated
- 2 years ago
Overview
Brief 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.
Detailed Description
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).
Investigators
Li Zhang, MD
Director
Sun Yat-sen University
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
- •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.
Arms & Interventions
Cohort 1: BRAF V600 mutation
Dabrafenib + Trametinib
Intervention: Dabrafenib + Trametinib
Cohort 2: MET ex14 skip mutation
Capmatinib
Intervention: Capmatinib
Outcomes
Primary Outcomes
Pathological complete response (pCR) rate
Time Frame: up to 2 years
pCR rate is defined as the percentage of participants with no residual viable tumor cells.
Secondary Outcomes
- Event-free survival (EFS)(up to 3 years)
- Disease-free survival (DFS)(up to 3 years)
- Overall survival (OS)(up to 3 years)
- Major pathological response (MPR) rate(up to 2 years)