Phase II Clinical Study of Befotertinib in EGFR Non-classical Mutant NSCLC

Phase 2

Recruiting

• Conditions: NSCLC (Non-small Cell Lung Cancer)
• Interventions: Drug: befotertinib

• Registration Number: NCT06863506
• Lead Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2024-10-01
• Status Verified: 2025-02
• Study First Submitted: 2025-03-03
• Study First Submitted QC: 2025-03-03
• Last Update Submitted: 2025-03-03
• Study First Posted: 2025-03-07
• Last Update Posted: 2025-03-07
• Primary Completion: 2027-06-30
• Study Completion: 2027-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 78

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
G719X, L861Q, or S768I)	befotertinib	Patients with EGFR uncommon mutations (G719X, L861Q, or S768I)
exon 20 insertion	befotertinib	Patients with EGFR exon 20 insertion mutations

Primary Outcome Measures

Name	Time	Method
Objective response rate (ORR) assessed by RECIST 1.1.	From enrollment until treatment discontinuation (up to 24 months)

Secondary Outcome Measures

Name	Time	Method
progression-free survival (PFS)	From first dose to disease progression or death (assessed up to 36 months)
Disease control rate (DCR)	From enrollment until treatment discontinuation (up to 24 months)
duration of response (DoR)	From the first documented response to disease progression or death, whichever occurs first, assessed up to 36 months.
overall survival（OS）	From enrollment until death from any cause, assessed up to 60 months. Survivors will be censored at the last follow-up

Trial Locations

Locations (1)

2nd Affiliated Hospital, School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China