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

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

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).

Study Overview

• Status: Recruiting
• Conditions: NSCLC (Non-small Cell Lung Cancer)
• Intervention / Treatment: Drug: befotertinib

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xia Yang; Phone Number: +86 18868439669; Email: yxia@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • 2nd Affiliated Hospital, School of Medicine
      • Contact: Xia Yang; Phone Number: +86 18868439669; Email: yxia@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: G719X, L861Q, or S768I); Patients with EGFR uncommon mutations (G719X, L861Q, or S768I)	Drug: befotertinib; Befotertinib will be administered orally at an initial dose of 75 mg once daily for 21 days, with escalation to 100 mg if tolerated. Treatment continues until disease progression, unacceptable toxicity, or withdrawal.
Experimental: exon 20 insertion; Patients with EGFR exon 20 insertion mutations	Drug: befotertinib; Befotertinib will be administered orally at an initial dose of 75 mg once daily for 21 days, with escalation to 100 mg if tolerated. Treatment continues until disease progression, unacceptable toxicity, or withdrawal.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: West China Hospital; Taizhou Hospital; The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital; Hunan Cancer Hospital - the Affiliated Cancer Hospital of Xiangya school of Medicine, Central South University
• Investigators: Principal Investigator: Li Wen, Prof., Second Affiliated Hospital, School of Medicine, Zhejiang University; Principal Investigator: Xia Yang, Prof., Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: March 3, 2025
• First Submitted That Met QC Criteria: March 3, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 3, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 2024-0190

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No