Evaluation of the Efficacy and Safety of Furmonertinib Combined with Bevacizumab As First-Line Treatment for EGFR-Positive Non-Small Cell Lung Cancer with Brain Metastases: a Single-Arm, Open-Label, Prospective Phase II Clinical Study

Study Purpose

This study evaluates the safety and efficacy of Befotertinib combined with Bevacizumab as a first-line treatment for patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC) accompanied by brain or leptomeningeal metastases. It is a single-arm, open-label, prospective Phase II clinical trial aiming to explore the potential benefits of this combination therapy in improving intracranial progression-free survival (iPFS) and overall survival (OS). Patients will receive Befotertinib daily and Bevacizumab every three weeks until disease progression, intolerable toxicity, or withdrawal of consent. The study seeks to address the unmet need for effective treatments in this challenging patient population.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 15 Years - 75 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Aged 18-75 years. ECOG performance status (PS) score of 0-2. Expected survival time of ≥3 months. 2. Histologically or cytologically confirmed non-squamous non-small cell lung cancer (NSCLC). 3. Baseline evaluation confirming the presence of EGFR-sensitizing mutations (19del/L858R) via first- or second-generation sequencing. Test samples can include archived tumor tissue or fresh tumor tissue collected during screening. If unavailable, pleural effusion, cerebrospinal fluid, or blood samples may be used for testing. 4. Asymptomatic brain metastases or those with controlled intracranial hypertension symptoms following dehydration treatment. Continued medication to maintain stable symptoms at enrollment or during the study is allowed. 5. For patients with parenchymal or leptomeningeal brain metastases, MRI must confirm at least one brain lesion with a diameter ≥5 mm. 6. No prior systemic anti-tumor therapy for locally advanced or metastatic NSCLC. Patients who underwent radical surgery, chemoradiotherapy, or adjuvant therapy (chemotherapy or radiotherapy) for early-stage NSCLC may be included if their disease recurred or metastasized after treatment, provided the interval from the last treatment to initial tumor recurrence exceeds 6 months. 7. Normal function of major organs, with the following criteria: Hematology (without transfusion or hematopoietic stimulating factors within 14 days): Hemoglobin (HB) ≥ 90 g/L. Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L. Platelets (PLT) ≥ 80 × 10⁹/L. Biochemistry: Total bilirubin (TBIL) < 1.5 × upper limit of normal (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 × ULN (if liver metastases are present, ALT and AST < 5 × ULN). Creatinine (Cr) ≤ 1.25 × ULN or creatinine clearance rate (CCr) ≥ 45 mL/min (using the Cockcroft-Gault formula). Proteinuria < 2+ (if baseline proteinuria ≥ 2+, a 24-hour urine protein quantification ≤ 1 g is required). International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN. Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%) as assessed by Doppler ultrasound. 8. Women of childbearing potential must agree to use effective contraception (e.g., intrauterine devices, oral contraceptives, or condoms) during the study and for 6 months after its completion. Negative serum or urine pregnancy test within 7 days prior to enrollment and non-lactating status are required. Male participants must agree to use contraception during the study and for 6 months afterward. 9. Participants must voluntarily consent to participate in the study, sign an informed consent form, and demonstrate good compliance.

Exclusion Criteria:

1. Active Bleeding with Brain and/or Leptomeningeal Metastases. 2. Includes therapies with agents such as bevacizumab, endurance, or anlotinib. 3. ≥ Grade 2 toxicity (NCI-CTCAE v4.03) related to prior treatments not resolved at the start of study treatment (excluding alopecia and Grade 2 neurotoxicity caused by platinum agents). 4. Includes uncontrolled nausea/vomiting, inability to swallow, gastrointestinal resection, chronic diarrhea, or intestinal obstruction. 5. Prior whole-brain radiotherapy (WBRT). Radiotherapy involving >30% of bone marrow or extensive radiation within 4 weeks before the first dose (palliative radiotherapy for non-brain metastases, such as bone metastases, is exempt). 6. Poorly controlled hypertension (defined as blood pressure ≥160/100 mmHg despite optimal antihypertensive therapy). Cardiac criteria, including: QTcF ≥ 470 msec (average of three ECGs, corrected using Fredericia's formula) at rest. Clinically significant arrhythmias, conduction abnormalities, or ECG changes (e.g., complete left bundle branch block, third-degree AV block, second-degree AV block, PR interval ≥250 msec). Factors increasing risk of QT prolongation or arrhythmias, such as NYHA Class III-IV heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age, or use of QT-prolonging medications. Active or uncontrolled severe infections. Liver disease, including cirrhosis, decompensated liver disease, or chronic active hepatitis. Poorly controlled diabetes (fasting blood glucose >10 mmol/L). Urinalysis showing ≥2+ proteinuria, confirmed by 24-hour urine protein quantification >1.0 g. 7. Presence of unhealed wounds or fractures. 8. NCI-CTCAE > Grade 1 pulmonary bleeding within 4 weeks before enrollment. NCI-CTCAE > Grade 2 bleeding at other sites within 4 weeks before enrollment. Bleeding tendencies (e.g., active gastrointestinal ulcers) or patients on thrombolytic or anticoagulant therapy (e.g., warfarin, heparin, or similar agents). 9. History of arterial/venous thrombosis within 12 months before enrollment, including stroke (e.g., transient ischemic attack, cerebral hemorrhage, or infarction), deep vein thrombosis, or pulmonary embolism. 10. Clinically significant hemoptysis (>50 mL/day) within 3 months before enrollment. Severe bleeding symptoms or conditions such as gastrointestinal bleeding, bleeding gastric ulcers, stool occult blood ≥2+, or vasculitis. 11. History of interstitial lung disease, drug-induced interstitial lung disease, steroid-requiring radiation pneumonitis, or clinically active interstitial lung disease. 12. History of substance abuse or uncontrolled psychiatric disorders. 13. Poorly controlled pleural or ascitic effusions despite symptomatic treatment, causing Grade ≥2 respiratory syndrome (≥CTCAE Grade 2). 14. Known active infections, including: Active hepatitis B (HBsAg positive and HBV-DNA ≥ 2 × 10³ IU/mL during screening). Hepatitis C (HCV-Ab positive and HCV-RNA positive during screening). Active tuberculosis (evidence of active infection within 1 year). Syphilis (both specific and non-specific antibodies positive). HIV infection (HIV antibody positive). Active infections are not routinely screened unless clinically indicated. 15. Severe diseases or conditions deemed to pose risks to patient safety or impede study completion. 16. Severe diseases or conditions deemed to pose risks to patient safety or impede study completion. 17. Prior allogeneic bone marrow transplantation. 18. Prior allogeneic bone marrow transplantation. 19)Any other condition deemed unsuitable for the study by the investigator. 20)Major surgery within 28 days before the first dose (defined as surgeries requiring at least 3 weeks of recovery before study treatment).

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT06728865
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Li-kun Chen
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries China
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Non-small Cell Lung Cancer (NSCLC), EGFR Mutation-Positive Lung Cancer, Brain Metastases, Leptomeningeal Metastases, Intracranial Tumor Progression
Arms & Interventions

Arms

Experimental: Furmonertinib Combined with Bevacizumab Treatment Group

The treatment regimen is Furmonertinib combined with Bevacizumab.

Interventions

Drug: - The treatment regimen is Furmonertinib combined with Bevacizumab.

The treatment regimen is Furmonertinib combined with Bevacizumab.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Sun Yat-sen University Cancer Center, Guang zhou, Guang dong, China

Status

Recruiting

Address

Sun Yat-sen University Cancer Center

Guang zhou, Guang dong, 510000

Site Contact

li kun Chen

[email protected]

13798019964

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