Clinical trial NCT06863506: Phase II Clinical Study of Befotertinib in EGFR Non-classical Mutant NSCLC
Official title: Prospective, Multi-cohort, Single-arm Phase II Clinical Study Evaluating the Efficacy and Safety of Befotertinib in EGFR-positive Non-classical Mutant Non-small Cell Lung Cancer Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: NSCLC (Non-small Cell Lung Cancer)
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
Collaborators: name: The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital
name: Hunan Cancer Hospital - the Affiliated Cancer Hospital of Xiangya school of Medicine, Central South University
name: Taizhou Hospital
name: West China Hospital
First posted: 2025-03-07
Enrollment: 78
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 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 criteria: 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

Primary outcomes:
measure: Objective response rate (ORR) assessed by RECIST 1.1.
timeFrame: From enrollment until treatment discontinuation (up to 24 months)
Secondary outcomes:
measure: progression-free survival (PFS)
timeFrame: From first dose to disease progression or death (assessed up to 36 months)
measure: Disease control rate (DCR)
timeFrame: From enrollment until treatment discontinuation (up to 24 months)
measure: duration of response (DoR)
timeFrame: From the first documented response to disease progression or death, whichever occurs first, assessed up to 36 months.
measure: overall survival（OS）
timeFrame: From enrollment until death from any cause, assessed up to 60 months. Survivors will be censored at the last follow-up
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: 2nd Affiliated Hospital, School of Medicine
state: Zhejiang
Study officials:
affiliation: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: Li Wen, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: Xia Yang, Prof.
role: PRINCIPAL_INVESTIGATOR
References: