An Observational Study of Furmonertinib for EGFR Mutation-positive NSCLC Patients With Brain Metastasis

Efficacy and Safety of Furmonertinib for Epidermal Growth Factor Receptor (EGFR) Sensitive Mutation Positive Non-Small Cell Lung Cancer (NSCLC) Patients With Brain Metastasis: a Prospective Observational Study

EGFR mutation positive advanced NSCLC patients with CNS metastases were associated with poor prognosis. Furmonertinib showed promising CNS efficacy in doses of 80 mg orally once daily or higher in patients with EGFR T790M mutation positive NSCLC. This study aims to investigate the efficacy and safety of furmonertinib in the treatment of EGFR-sensitive mutation positive NSCLC patients with brain metastasis.

Study Overview

• Status: Recruiting
• Conditions: EGF-R Positive Non-Small Cell Lung Cancer; CNS Metastases
• Intervention / Treatment: Drug: Furmonertinib

Detailed Description

This study aims to prospectively observe the efficacy and safety of furmonertinib in the treatment of EGFR-sensitive mutation positive NSCLC patients with brain metastasis and will recruit about 30 patients in China.

Furmonertinib (AST2818) is a brain penetrant third generation EGFR TKI. In preclinical studies, the concentration of furmonertinib and its main active metabolite in the brain was higher than that in the plasma, indicating that furmonertinib had the potential to treat CNS metastases. Furmonertinib showed promising CNS efficacy in doses of 80 mg orally once daily in patients with EGFR T790M mutated NSCLC, the median CNS PFS was 11.6 months and 19.3 months in the 80 mg and 160 mg orally once daily group, and the CNS ORR was 65% and 85% in the 80 mg and 160 mg group.

This study will enroll the EGFR-sensitive mutation positive NSCLC patients with brain metastasis who are treated by furmonertinib, and the efficacy and safety data will be recorded.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Haichuan Su, PhD; Phone Number: 18629190366; Email: such@fmmu.edu.cn
• Study Contact Backup: Name: Jie Min, PhD; Phone Number: 13709202616; Email: minjie1504@163.com

Study Locations

• China
  • Shanxi
    • Xi'an, Shanxi, China, 710038
      • Recruiting
      • Tangdu Hopspital
      • Contact: Haichuan Su, PhD; Phone Number: 18629190366; Email: such@fmmu.edu.cn
      • Contact: Jie Min, PhD; Phone Number: 13709202616; Email: minjie1504@163.com
      • Principal Investigator: Haichuan Su, PhD
      • Sub-Investigator: Jie Min, PhD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patient with EGFR 19Del or L858R mutation diagnosed histologically or cytologically and imaging (MR/CT) confirmed untreated brain metastases before Furmonertinib initiation.

Description

Inclusion Criteria:

1. at least 18 years of age;
2. Histologically or cytologically confirmed metastatic non-squamous Non-Small Cell Lung Cancer (NSCLC);
3. Patient with EGFR 19Del or L858R mutation diagnosed histologically or cytologically.( EGFR L858R or Del 19 with/without T790M )
4. Imaging (MR/CT) confirmed untreated brain metastases before Furmonertinib initiation;
5. Organ function is compatible with oral Furmonertinib therapy (investigator determination based on real-world practice);
6. Life expectancy ≥12 weeks before Fumonertinib initiation;
7. ECOG PS of 0 to 2;
8. Sign the informed consent form.

Exclusion Criteria:

1. Any Third-Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) before Furmonertinib initiation;
2. Known hypersensitivity to Furmonertinib or its excipient components;
3. Simultaneous systemic chemotherapy or WBI;
4. The time from the treatment with any other investigational product or its analogue before Furmonertinib initiation does not exceed 5 half-lives of the drug or 14 days, whichever is longer;
5. Any evidence of severe or uncontrolled systemic diseases;
6. Presence of any disease that may strongly interfere with oral drug absorption; presence of any factor that contributes to QTc prolongation or increased risk of arrhythmia; presence of interstitial pneumonitis.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Furmonertinib group; Patients treated with Furmonertinib	Drug: Furmonertinib; Patients treated with Furmonertinib mesilate tablets orally; Other Names: AST2818

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial Objective response rate	Per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) using Investigator assessments, is defined as the number (%) of patients with CNS lesion response of Complete Response or Partial Response, will be assessed up to 2 years.	Data obtained up until progression, or the last evaluable assessment in the absence of progression, will be assessed up to 2 years.
Intracranial Disease Control Rate	The percentage of subjects who have a best CNS lesion response of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by the Investigator, will be assessed up to 2 years.	Data obtained up until progression, or the last evaluable assessment in the absence of progression, will be assessed up to 2 years.
Intracranial progression-free survival	Intracranial progression-free survival (PFS) analysis based on investigator assessment and will be assessed up to 3 years.	Intracranial progression-free survival (PFS) analysis based on investigator assessment and will be assessed up to 3 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Progression-free survival (PFS) is defined as the time from first dose of Furmonertinib recorded until the date of disease progression based on investigator assessment.	Progression-free survival (PFS) analysis based on investigator assessment per RECIST 1.1, and will be assessed up to 2 years.
Overall Survival	Overall survival is defined as the time from beginning of furmonertinib treatment until death due to any cause and will be assessed up to 3 years.	The time from beginning of furmonertinib treatment until death due to any cause and will be assessed up to 3 years.
Safety/Adverse event	Incidence of Adverse Events (AEs): Incidence, severity and seriousness of adverse events, incidence of serious adverse events (SAEs), which usually be graded by CTCAE v5.0 based on current clinical practice.	From the recorded first dose of Furmonertinib to 4 weeks after the recorded last dose of Furmonertinib

Collaborators and Investigators

• Sponsor: Tang-Du Hospital
• Investigators: Principal Investigator: Haichuan Su, PhD, Tang-Du Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2022
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): September 30, 2024

Study Registration Dates

• First Submitted: March 7, 2024
• First Submitted That Met QC Criteria: April 2, 2024
• First Posted (Actual): April 8, 2024

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC; EGFR; CNS metastases; Furmonertinib
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Brain Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Aflutinib
• Other Study ID Numbers: 202112-28

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No