Furmonertinib in EGFR-Mutant NSCLC With Brain Metastases (iFORCE)

Efficacy and Safety of Furmonertinib in Patients With EGFR Mutations in Advanced NSCLC With Brain Metastases: A Prospective, Open-label, Phase II Trial（iFORCE）

This study is a single-arm, open-label, prospective phase II trial. The aim of this phase II study is to evaluate the efficacy and safety of Furmonertinib in patients with EGFR mutation (including 19del or 21L858R or T790M) in advanced NSCLC with brain metastases.

Study Overview

• Status: Completed
• Conditions: NSCLC; Brain Metastases; Furmonertinib; EGFR-mutation
• Intervention / Treatment: Drug: Furmonertinib 160 mg, Q.D.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100021
    • Ethics Committee

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1.Male or Female aged ≥18 years old; 2.ECOG PS 0-2; 3.Histologically or cytopathologically confirmed non-small cell lung cancer (NSCLC) ; Tumor tissue samples or blood samples are confirmed to be EGFR mutations (including 19del or 21L858R or T790M); 4.Patients with brain metastases previously treated (chemotherapy, TKI), or intracranial progression after brain radiotherapy； 5.Life expectancy >3 months; 6.Without meningeal metastases; 7.According to mRECIST, the subject has at least 1 intracranial measurable lesion (≥ 5mm); 8.Adequate organ function (28 days before enrollment), including:

1. Blood routine examination HB≥90 g/L（No blood transfusion within 14 days prior to enrollment） ANC≥1.5×109 /L PLT≥100×109 /L
2. Biochemical examination TBIL≤1.5 times ULN AST and ALT≤2.5 times ULN (with liver metastasis, AST and ALT≤5 times ULN) Cr≤1×ULN，CrCL ≥50 mL /min (according to Cockcroft-Gault formula) PT/INR≤1.5 times ULN; aPTT≤1.5 times ULN (If the subject is receiving anticoagulation, PT or aPTT is within the therapeutic range expected for anticoagulant use) 9.No systemic corticosteroid therapy within 4 weeks prior to treatment; 10.Males of reproductive potential or females of potential pregnancy must take effective contraceptive measures (eg, oral contraceptives, intrauterine devices, abstinence or barrier contraception combined with spermicide) during the study and and within 12 months after drug discontinuation; 11.Being able to understand and voluntarily participate in the study, and sign the informed consent form, with good compliance and for follow-up.

Exclusion Criteria:

1.Known or suspected allergy to Furmonertinib or other components; 2.With EGFR Ex20ins mutation; 3.Subjects who have received other anti-tumor therapy within four weeks prior to the first dose of the study or who have failed to recover (≤ grade 1) from an adverse event resulting from prior treatment; 4.Any of the following cardiac criteria:

1. QTc>470 ms on ECG at resting state, when the first abnormality occurs, the test is repeated 2 times within 48h, and the average result of 3 times is calculated.
2. Various clinically significant abnormalities in rhythm, conduction, and resting ECG patterns, such as complete left bundle branch block, third-degree atrioventricular block, second-degree atrioventricular block, PR interval >250msec, etc.
3. Factors that may increase the risk of QTc prolongation or the risk of arrhythmic events.

5.Pregnant or breastfeeding women; 6.Known hepatitis C virus (positive HCV Ab) or human immunodeficiency virus (positive HIV antibody) infection, positive HBsAg or HBCAb with positive HBV DNA copy number (>500 IU/ml); 7.Previous interstitial lung disease (ILD); 8.Having severe or uncontrolled systemic disease, including active opportunistic infection or progressive (severe) infection, uncontrolled diabetes, cardiovascular disease (III or IV heart failure by NYHA Functional Classification, second degree or greater atrioventricular block, myocardial infarction or unstable arrhythmia or unstable angina within the past 6 months, cerebral infarction within 3 months, etc.), pulmonary disease (interstitial pneumonia, obstructive pulmonary disease and history of symptomatic bronchospasm); 9.Meningeal metastases. Intracranial metastases with CNS symptoms may be enrolled if the metastases can be adequately treated and CNS symptoms can be restored to a level less than or equal to CTCAE1 and remain stable prior to enrollment; 10.Received a live vaccination within 4 weeks prior to the start of study treatment; 11.Major surgery (excluding diagnostic surgery) within 4 weeks prior to the start of treatment; 12.Known history of mental disease or drug abuse, and currently having an attack or still taking drugs; 13.Serious gastrointestinal dysfunction, or disease that may affect the intake, transportation or absorption of investigational product; 14.History of other malignant tumors within 3 years, except for cured basal cell carcinoma and cervical carcinoma in situ; 15.According to the investigators, subjects with other serious acute or chronic disease, mental disease , laboratory abnormalities that may increase the risk or interfere with the interpretation of study results are excluded; 16.Subjects who are or have been involved in other clinical studies within 4 weeks; 17.According to the investigator, subjects may not complete this study or may not comply with the requirements of this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: previously treated; advanced NSCLC previously treated with systemic therapy, including chemotherapy and targeted therapy	Drug: Furmonertinib 160 mg, Q.D.; Furmonertinib 160 mg orally once daily in previously treated groups

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial Progression Free Survival (iPFS)	The time from the first does of the study drugs to the intracranial progression of the disease or death for any reason.	Approximately 18 months after the first patient begin study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Proportion of subjects whose tumors were assessed as complete response(CR) or partial response(PR) according to RECIST 1.1.	Approximately 12 weeks following the first dose of study drug
Disease Control Rate (DCR)	Proportion of subjects whose tumors were assessed as CR, PR or stable disease (SD) according to RECIST 1.1.	Approximately 18 months from the first patient begin study treatment
Disease progression free survival (PFS)	The time from the first does of the study drugs to the progression of the disease or death for any reason.	Approximately 18 months after the first patient begin study treatment
Overall survival (OS)	The time from the first does of the study drugs to the death for any reason.	Approximately 24 months after the first patient begin study treatment
Adverse Events (AEs)	The number of patients with adverse events and the severity according to CTCAE v5.0	From the start of study drug to 28 days after the last dose of study drug
Intracranial Objective Response Rate (iORR)	Proportion of subjects whose intracranial tumors were assessed as complete response(CR) or partial response(PR) according to mRECIST.	Approximately 12 weeks after the first patient begin study treatment
Intracranial Disease Control Rate (iDCR)	Proportion of subjects whose intracranial tumors were assessed as complete response(CR), partial response(PR), or stable disease(SD) according to mRECIST.	Approximately 18 months from the first patient begin study treatment

Collaborators and Investigators

• Sponsor: Peking Union Medical College
• Investigators: Principal Investigator: Junling Li, Professor, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2022
• Primary Completion (Actual): December 12, 2025
• Study Completion (Actual): December 12, 2025

Study Registration Dates

• First Submitted: July 15, 2022
• First Submitted That Met QC Criteria: July 15, 2022
• First Posted (Actual): July 19, 2022

Study Record Updates

• Last Update Posted (Estimated): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 14, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms; aflutinib
• Other Study ID Numbers: NCC3050

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