Overview
This is a prospective, multi-cohort, single-arm Phase II clinical trial evaluating the efficacy and safety of befotertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), in patients with advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR non-classical mutations.
The study comprises two independent cohorts:
Cohort 1: Patients with EGFR uncommon mutations (G719X, L861Q, or S768I). Cohort 2: Patients with EGFR exon 20 insertion mutation
Primary endpoint: Objective response rate (ORR) assessed by RECIST 1.1. Secondary endpoints: Disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety profile (CTCAE v4.03).
Eligibility
Inclusion Criteria:
- Age ≥18 years, ECOG performance status 0-2
- Histologically confirmed locally advanced/metastatic NSCLC
- Documented EGFR mutations: Cohort 1 (G719X/L861Q/S768I) or Cohort 2 (exon 20 insertion)
- No prior EGFR-TKI therapy
- Progression or intolerance to ≥1 line of platinum-based chemotherapy -≥1 measurable lesion per RECIST 1.1
Exclusion Criteria:
- Previous EGFR-TKI treatment
- Active CNS metastases (asymptomatic patients with stable lesions allowed)
- Severe cardiovascular disease (e.g., QTc ≥450 ms, myocardial infarction within 6 months)
- Active HBV/HCV/HIV infection
- Pregnancy or lactation