High-dose Furmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed Chemotherapy in Patients With EGFR-mutated Non-small Cell Lung Cancer and Meningeal Metastasis

Sun Yat-sen University

Status and phase: Enrolling; Phase 2

Conditions: Non-small Cell Lung Cancer Metastatic

Treatments: Drug: furmonertinib

Study type: Interventional

Funder types: Other

Identifiers

NCT06812871

GASTO 10120

Details and patient eligibility

About

the study conducted to evaluate the efficacy and safety of high-dose furmonertinib (160 mg qd) combined with bevacizumab and pemetrexed intrathecal chemotherapy in NSCLC patients with EGFR mutations and meningeal metastases.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histological or cytological localization is NSCLC;
• confirmed EGFR exon 19 deletion mutation(19del) or EGFR exon 21L858R mutation (L858R) or EGFR exon 20 T790M mutation (T790M)）;
• Clinical diagnosis of meningeal aggravation: clinical symptoms of intracranial hypertension (headache, dizziness, vomiting, etc.) + imaging confirmation (cerebral MRI diagnosis of meningeal aggravation) or cerebrospinal fluid cytology confirmation;
• for patients with symptoms who are considered to need temporary brain local. Treatment of cough receiving adrenal corticosteroids must be kept stable or reponse for at least 1 week before the first trial of the drug preparation;
• Newly diagnosed meningeal metastasis, including meningeal metastasis after previous brain surgery and/or local radiotherapy for solid metastatic disease;
• Patients had not received previous systemic treatment for advanced NSCLC or had meningeal metastases after treatment with one third-generation EGFR-TKI.
• Obtain informed consent signed by the patient's legal representative;
• Aged ≥18 years and ≤75 years;
• Eastern Tourism Cooperation Group (ECOG) Physical condition evaluation 0-1;
• Life expectancy ≥12 week;
• Able to follow the requirements of the study protocol and confirmation procedures, and able to accept cranial wall medications;
• contraception.

Exclusion criteria

• Mixed non-small cell and small cell carcinoma, or squamous cell carcinoma as the main pathological type;

• Known EGFR exon 20 C797X mutation (C797X);

• history of hypersensitivity reaction to active or inactive excipients of furmonertinib, bevacizumab or pemetrexed or to drugs of similar structure or class to the investigational drug;

• Brain metastases have previously received whole-brain radiotherapy;

• Currently participating in an interventional clinical trial, or having received other study drugs or study devices within 4 weeks before the first study drug;

• Patients who have received solid organ or blood system transplantation;

• Patients with severe intracranial hypertension symptoms that cannot be relieved by discontinuation of dexamethasone and/or glycol treatment, or patients in intensive care;

• Ensure control of the patient's symptomatic pericardial, peritoneal, and pleural effusions;

• History of cancer in the last five years Other malignancies or a history of other malignancies;

• Recent active digestive events, such as duodenitis, ileitis, intestinal perforation, intestinal catheters, or other conditions that may cause gastrointestinal tract or perforation; or refractory vomiting, chronic gastrointestinal disease, inability to swallow study drugs, or previous colorectal cancer resection that prevents adequate drug absorption;

• The patient has a physique that is prone to Japanese language learning or has active Japanese language learning;Central squamous cell carcinoma orPatients at greater risk for hemoptysis; Any diamond event ≥ CTCAE grade 3, presence of open wounds, injuries or fractures in the 28th century before the first creation; if in the first Asthma was accepted 28 days before the organization meeting, the wound treatment should be evaluated by the interval period;

• History of arterial thromboembolism within the last 6 months, including vascular cerebral accident, myocardial infarction, transient cerebral contemplation;

• History of grade 4 venous thrombosis within the last 6 months, including fire embolism;

• The presence of any severe or uncontrolled systemic evidence, including difficult-to-control hypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg), uncontrolled diabetes, etc.;

• Active infections include, for example, hepatitis B, hepatitis C, and human immunodeficiency virus (HIV) infections (including those requiring intravenous therapy, active hepatitis B infection includes patients with positive hepatitis B surface test based on serological assessment and hepatitis B virus DNA >1000 copies/ml);

• previous history of interstitial lung disease, drug-induced interstitial lung disease, pneumonitis requiring steroid therapy, or any evidence of active interstitial lung disease;

• The first 28-day inspection of the drug preparation showed Lack of adequate bone marrow reserve or organ function（Within 2 weeks before blood test,No blood transfusion or blood products, granulocyte colony-stimulating factor or other hematopoietic stimulating factors were used for repair）:

  • Absolute neutrophil count <1.5 × 109/L; continuous count <100×109/L; hemoglobin <90 g/L;
  • Alanine aminotransferase > 2.5 times Upper limit of normal value (Upper limit of normal）; Aspartate aminotransferase>2.5 times ULN; Total bilirubin>1.5 times ULN;or liver transplant patients with AST and/or ALT > 5× ULN;
  • Albumin <30 g/L;
  • Serum creatinine >1.5 times ULN, and Creatinine clearance <50 mL/min（Measured or calculated by Cockcroft and Gault formula);
  • International normalized ratio (INR) > 1.5,Partially activated zymogen time（APTT>1.5 times Upper limit of normal;
  • Urine protein ≥++, and 24-hour protein >2.0g;

• Any of the following Bishop criteria:

  • Clinically significant resting electrocardiogram rhythm, respiratory, or morphological abnormalities, such as left bundle branch block, third-degree myocardial insufficiency, and second-degree myocardial insufficiency, within 28 days before the first study drug perfume;
  • Possibility Interphase Factors that increase the risk of prolonged or arrhythmic events, such as heart failure, congenital long Quantum Dots Syndrome, long Quantum Dots Family history or first-degree relatives 40 Sudden death due to coma or known prolonged Quantum Dots Any sudden or difficult to fully compensate low potassium tariffs, low tariff tariffs, and low tariff-to-tariff tariffs during the period;
  • Left ventricular ejection fraction (LVEF)Left ventricular ejection fraction）<50%, recent History of myocardial infarction, severe or unstable angina, or coronary artery bypass grafting within the past month or heart failure≥New York Heart Association (New York Heart Association (NYHA) 2 class;

• Pregnancy or breastfeeding.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Furmonertinib combined with bevacizumab and intrathecal pemetrexed chemotherapy

Experimental group

Description:

patients receive furmonertinib (160mg, once a day) combined with bevacizumab (7.5 mg/kg, once every 3 weeks) and pemetrexed (50 mg intrathecal injection chemotherapy, once every 3 weeks, up to 9 cycles).

Treatment:

Drug: furmonertinib