NSCLC with T790M+ brain metastases that progressed after first- and second-generation TKI treatment, and T790M+ brain metastases after first- and second-generation TKI treatment
Conditions
Interventions
Group one:Furmonertinib 160mg
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Provide informed consent prior to any study of specific procedures; 2. Aged 18 and above; 3. Lung adenocarcinoma confirmed histologically or cytologically by biopsy performed within 60 days prior to study enrollment; 4. EGFR mutation positive (exon 19 deletion or exon 21 L858R) without prior EGFR-TKI treatment and confirmed by any participating center approved gene testing method (ARMS, DD-PCR, NGS, etc.); Or patients were confirmed positive for EGFR T790M mutation after egFR-TKI 1 /2 /3 generation treatment by any of the participating centers approved gene testing methods (ARMS, DD-PCR, NGS, etc.); 5. Presence of at least one accurately measurable intracranial metastatic lesion with a maximum diameter of >=10mm on computed tomography (CT) or magnetic resonance imaging (MRI) at baseline and suitable for accurate repeat measurement 6.The patient progresses intracranially without related symptoms, or has symptoms but is stable for 4 weeks after local treatment; 7. ECOG physical status is 0-2 points; 8. Hematology and liver and kidney function are adequate for drug treatment; 9. At least 2 weeks before starting the study drug, female subjects should use highly effective contraceptive measures, the pregnancy test must be negative, and there is no ongoing breastfeeding before starting the drug, or otherwise, one of the following criteria must be met at the time of screening to prove the possibility of infertility: (1) Postmenopausal is defined as the age over 50 years old, and amenorrhea for at least 12 months after stopping all exogenous hormone treatments; (2) Women under the age of 50 who stop menopause for 12 months or more after stopping exogenous hormone therapy and have LH and FSH levels within the postmenopausal range of the institution should be considered as menopausal; (3) Irreversible surgical sterilization recorded by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but does not include tubal ligation; 10. Male subjects must be willing to use barrier contraception; 11. Able to comply with the requirements of the research protocol and follow-up procedures, and be able to receive oral medication.
Exclusion criteria
Exclusion criteria: 1. Tumors with neuroendocrine components such as large cell carcinoma or small cell carcinoma 2. Confirmed EGFR exon 20 insertion mutation or EGFR C797X mutation; 3. Exposure to other anti-tumor treatments before enrollment (the washout period is at least 5 half-lives of the applied drug); 4. The patient is pregnant or breastfeeding; 5. Currently receiving (or cannot stop using it before receiving the first dose of study treatment) drugs or herbal supplements that are known to be potent inducers of CYP3A4 (at least 3 weeks ago). All patients must try to avoid concomitant use or ingestion of any drugs, herbal supplements and/or foods that are known to have an inducing effect on CYP3A4. 6. Evidence of any severe or uncontrolled systemic disease, including uncontrolled hypertension and active bleeding, which the investigator believes is not conducive to the patients participation in the study or undermining the compliance of the protocol, or including hepatitis B, hepatitis C Active infections including human immunodeficiency virus (HIV). Screening for chronic diseases is not a requirement. 7. Any of the following cardiac standards: (1) Using the QTc value obtained by the screening clinics electrocardiograph, the average resting-corrected QT interval (QTc) obtained from 3 electrocardiogram (ECG) examinations is> 500 milliseconds, (2) Any clinically significant resting ECG rhythm, conduction, or morphological abnormalities, such as left bundle branch block, third-degree heart block, and second-degree heart block (3) Any factors that increase the risk of QTc prolongation or arrhythmia events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medications in first-degree relatives under the age of 40 who die suddenly of unknown cause or are known to prolong the QT interval (4) Cardiac function assessment: Left ventricular ejection fraction (LVEF) = New York Heart Association (NYHA) in the last 6 months ) Level 2 8. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy, or any evidence of active interstitial lung disease. 9. Lack of adequate bone marrow reserve or organ function (proved by any of the following laboratory values: absolute neutrophil count 2.5 times ULN; aspartate aminotransferase>2.5 times ULN (for patients with liver metastases, this index can reach 5 times the upper limit of normal); total bilirubin>1.5 times ULN; serum creatinine>1.5 times ULN, With creatinine clearance rate 1.5 times ULN, only creatinine clearance rate needs to be confirmed). 10. History of hypersensitivity reactions to active or inactive excipients of Furmonertinib or drugs with similar chemical structure or class to Furmonertinib 11. Uncontrollable nausea and vomiting, chronic gastrointestinal disease, inability to swallow formulated medicines, or previous large bowel resections that would prevent adequate absorption of Furmonertinib 12. Evaluate any evidence of corneal injury confirmed by ophthalmological examination by a slit lamp. 13. Patients who have undergone alloge
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| iORR: Objective response rate for intracranial lesions;iPFS: progression-free survival in intracranial lesions;ORR: objective response rate;PFS: progression-free survival; | — |
Secondary
| Measure | Time frame |
|---|---|
| DCR: Disease Control Rate;DOR: Duration of relief;Overall survival at 12 months (1-year OS rate); | — |
Countries
China
Contacts
Public ContactYouling Gong
West China Hospital of Sichuan University
Outcome results
None listed