Neoadjuvant and Adjuvant Targeted Treatment in NSCLC With BRAF V600 or MET Exon 14 Mutations

NCT ID: NCT06054191

Last Updated: 2023-10-10

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-01
• Study Completion Date: 2027-03-01

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).

Conditions

NSCLC; BRAF V600 Mutation; MET Exon 14 Mutation

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: BRAF V600 mutation

Dabrafenib + Trametinib

Group Type: EXPERIMENTAL

Dabrafenib + Trametinib

Intervention Type: DRUG

Dabrafenib 150mg BID + Trametinib 2mg QD/（2 cycles）

Cohort 2: MET ex14 skip mutation

Capmatinib

Group Type: EXPERIMENTAL

Capmatinib

Intervention Type: DRUG

Capmatinib 400mg BID/（2 cycles）

Interventions

Dabrafenib + Trametinib

Dabrafenib 150mg BID + Trametinib 2mg QD/（2 cycles）

Intervention Type: DRUG

Capmatinib

Capmatinib 400mg BID/（2 cycles）

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Li Zhang, MD

Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Cancer Center of Sun-Yat Sen University

Guangzhou, Guangdong, China

Countries

China

Central Contacts

Li Zhang, MD

Role: CONTACT

zhangli6@mail.sysu.edu.cn

86-20-87343458

Other Identifiers

B2023-331-01

Identifier Type: -

Identifier Source: org_study_id