Lung cancer
Conditions
Interventions
EGFR20 insertion mutation :Sunvozertinib combined with anlotinib hydrochloride
EGFR non-classical mutation:Sunvozertinib combined with anlotinib hydrochloride
Sponsors
Cancer Hospital, Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age: 18-75 years old. 2. Histologically or cytologically confirmed locally advanced or stage IV non-small cell lung cancer, Cohort 1 subjects were not treated systematically for locally advanced or stage IV disease, and Cohort 2 subjects were treated after first-line standard therapy for locally advanced or stage IV disease 3. Brain metastases are asymptomatic or do not require steroid hormone treatment; 4. EGFR 20 insertion mutation was confirmed by genetic testing of tumor tissue or samples of blood, pleural fluid, cerebrospinal fluid (cohort 1). EGFR non-classical mutations, including non-classical mutations such as G719X, S768I, L861Q, or complex mutations of non-classical mutations except exon insertion mutations of EGFR 20 (Cohort 2). 5. ECOG score 0-2 points; 6. Expected survival =3 months; Seven. Left ventricular ejection fraction (LVEF) was =50%. 8. The bone marrow function, liver and kidney function of the patient met the following requirements through laboratory examination before the first medication: (1) Neutrophil count (ANC) = 1,500/mm3 (1.5×109/L); (2) Platelet count (PLT) = 100,000/mm3 (100×109/L); Hemoglobin (Hb) = 9 g/dL (90 g/L); (4) Serum creatinine (SCr) = 1.5 times the upper limit of normal (ULN) or creatinine clearance = 60 ml/min; (5) Total bilirubin (TBIL) = 1.5 times the upper limit of normal value (ULN); (6) aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level = 2.5 times the upper limit of normal value (ULN), liver metastasis patients should = 5×ULN; (7) International Standardized ratio (INR) = 1.5, prothrombin time (PT) and activated partial thromboplastin time (APTT) = 1.5 times ULN; (8) Urinary protein <2+; If the urinary protein is =2+, the 24-hour urinary protein quantitative display of protein must be =1g; 9. The subjects voluntarily joined the study, signed the informed consent, had good compliance, and cooperated with the prevention
Exclusion criteria
Exclusion criteria: 1. Have uncontrolled or severe cardiovascular disease, such as refractory angina or congestive heart failure in the 6 months prior to screening; Myocardial infarction occurred within 12 months before screening; Any history of clinically significant ventricular arrhythmias or prolonged QT interval; Coronary heart disease with a history of cerebrovascular accidents, symptoms and medical treatment; 2. EGFR classical sensitive mutations, such as EGFR19 exon deletion mutation, EGFR 21 exon L858R point mutation and EGFR 20 exon T790M mutation; 3. Have significant digestive tract dysfunction that may affect the intake, transport, or absorption of oral drugs (e.g. inability to swallow, chronic diarrhea, intestinal obstruction, etc.); 4.3 Patients with a history of active bleeding, clinically significant bleeding symptoms, and definite bleeding tendency within the past months, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, stool occult blood + or above at baseline, vasculitis, etc.; 5.4 Received major surgery or severe traumatic injury, fracture, or poorly healed wound within the past week; 6. Significant respiratory history such as bronchiectasis, chronic obstructive pulmonary disease, pulmonary abscess, pulmonary embolism, etc. Seven. Active severe clinical infection (> NCI-CTCAE, version 5.0 Standard for Grade 2 infection); 8. Symptomatic meningeal metastasis; 9. Combined with previously untreated tumors other than primary lung cancer; 10. Participating in clinical trials of other drugs or antitumor drug therapy within 4 weeks prior to study initiation; 11. Previous treatment with other EGFR TKI and/or antivascular therapy; 12. Exclusion criteria related to the use of allotinib, including but not limited to: 1) Cavity-type squamous cell carcinoma or imaging evidence of macrovascular invasion/invasion were evaluated by researchers as having bleeding tendencies 2) History of hemoptysis within 3 months prior to first administration (2 tablespoons of bright red blood each time) 3) A history of bleeding disease or a history of bleeding disease without the use of therapeutic anticoagulants 4) Patients with bleeding tendencies (e.g. active digestive ulcers) or treated with anticoagulants or vitamin K antagonists such as warfarin, heparin, or their analogitics; Prophylactic use of low-dose warfarin (=1mg/d), low-dose heparin (= 12,000 U/d) or low-dose aspirin (=100mg/d) is permitted under the condition that INR =1.5; 5) Severe arteriovenous thrombosis events, such as cerebrovascular accidents (including temporary ischemic attacks), deep vein thrombosis and pulmonary embolism, occurred within 6 months before the first medication; 6) Vascular disease (such as aneurysms requiring treatment) within 6 months before the first dose 7) Venous thromboembolism with CTCAE = 3 8) Poorly controlled severe hypertension (systolic blood pressure = 140 mmHg and/or diastolic blood pressure = 90 mmHg) 9) A history of hypertensive crisis or hypertensive encephalopathy 10) A history of gastrointestinal perforation or fistula within 6 months prior to initial administration 11) Cerebral hemorrhage, including tumor related brain metastases 12) History of central nervous system disorders unrelated to the tumor (e.g., convulsions) 13) History of severe proteinuria (such as urine test paper = 2+ or 24h urine protein > 1 g) 13. Allergic to the investigational drug; 14. The patient has a serious concomitant medical condition, or any other condition in which the in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ORR; | — |
Countries
China
Contacts
Public ContactYan Wang
Cancer Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed