Clinical trial NCT06054191: Neoadjuvant and Adjuvant Targeted Treatment in NSCLC With BRAF V600 or MET Exon 14 Mutations
Official title: A Phase II, Two Parallel Group Study of Neoadjuvant and Adjuvant Targeted Treatment in NSCLC With BRAF V600 or MET Exon 14 Mutations
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: NSCLC
BRAF V600 Mutation
MET Exon 14 Mutation
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2023-09-26
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Pathological complete response (pCR) rate
timeFrame: up to 2 years
Secondary outcomes:
measure: Major pathological response (MPR) rate
timeFrame: up to 2 years
measure: Event-free survival (EFS)
timeFrame: up to 3 years
measure: Disease-free survival (DFS)
timeFrame: up to 3 years
measure: Overall survival (OS)
timeFrame: up to 3 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Cancer Center of Sun-Yat Sen University
state: Guangdong
Study officials:
References: