NSCLC
Conditions
Interventions
Treatment Group:Ivonescimab Combined with Chemotherapy
Sponsors
Cancer Hospital of Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Subjects are able to understand and voluntarily sign the written Informed Consent Form (ICF); 2. Age: 18 to 75 years; 3. Histologically or cytologically confirmed Stage IV non-small cell lung cancer (NSCLC); asymptomatic brain metastasis is allowed for enrollment; 4. Genetically confirmed by tumor tissue, blood, pleural effusion, or other specimen testing to have EGFR uncommon mutations, excluding exon 20 insertion mutations; 5. Progression after first-line first- or second-generation EGFR-TKI therapy with no emergence of T790M mutation after progression, or progression after first-line third-generation EGFR-TKI therapy; progression during adjuvant targeted therapy after surgery is allowed for enrollment; 6. ECOG performance status of 0-2; 7. Life expectancy >= 3 months; 8. At least one measurable lesion according to RECIST v1.1; 9. Prior to the first dose, laboratory tests confirm that the patient has adequate bone marrow, liver, kidney, and coagulation functions meeting the following requirements: a. Absolute neutrophil count (ANC) >= 1,500/mm³ (1.5×10?/L); b. Platelet count (PLT) >= 100,000/mm³ (100×10?/L); c. Hemoglobin (Hb) >= 9 g/dL (90 g/L); d. Creatinine clearance rate >= 60 mL/min; e. Total bilirubin (TBIL) <= 1.5 times the upper limit of normal (ULN); f. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level <= 2.5 times ULN; for patients with liver metastasis, AST and ALT should be <= 5×ULN; g. International normalized ratio (INR) <= 1.5, prothrombin time (PT), and activated partial thromboplastin time (APTT) <= 1.5 times ULN; 10. Cooperate with regular follow-up and adhere to the trial requirements.
Exclusion criteria
Exclusion criteria: 1. Histologically or cytologically confirmed presence of small cell carcinoma or squamous cell carcinoma components; 2. Harboring EGFR classic sensitive mutations, such as EGFR exon 19 deletion mutations and EGFR exon 21 L858R point mutations; or EGFR exon 20 insertion mutations; 3. Prior receipt of any immunotherapy targeting tumor immune mechanisms, including immune checkpoint inhibitors (e.g., anti-PD-1/L1 antibodies, anti-CTLA-4 antibodies, anti-LAG-3 antibodies, etc.), immune checkpoint agonists (e.g., antibodies against ICOS, CD40, CD137, GITR, OX40, etc.), immune cell therapies, etc.; first-line use of pemetrexed combined with platinum-based chemotherapy regimen; disease progression during postoperative adjuvant chemotherapy or adjuvant immunotherapy (these subjects are not eligible for enrollment); 4. Subjects with symptomatic brain metastasis, meningeal metastasis, or spinal cord compression; 5. History of severe bleeding tendency or coagulation dysfunction; presence of clinically significant bleeding symptoms within 1 month prior to the first dose, including but not limited to gastrointestinal bleeding, hemoptysis (defined as coughing up or spitting out =1 teaspoon of fresh blood or small blood clots, or coughing up blood only without sputum; subjects with blood-streaked sputum are allowed for enrollment), nasal bleeding (excluding epistaxis and retronasal bloody discharge), etc.; 6. Imaging during screening shows the tumor encasing surrounding vital organs and vessels or presence of obvious necrosis or cavities, and the investigator determines that participation in the study would pose a risk of bleeding; 7. Subjects with uncontrollable and requiring repeated drainage of pleural effusion, pericardial effusion, or ascites (subjects who do not require drainage of effusion or have a drainage frequency of less than once per month are eligible for enrollment); 8. Severe comorbidities, such as uncontrolled or severe cardiovascular diseases, e.g., history of myocardial infarction, unstable angina, or congestive heart failure within 3 months prior to the first dose; any history of clinically significant ventricular arrhythmia, QT interval prolongation; symptomatic coronary artery disease requiring drug therapy, etc.; occurrence of any arterial thromboembolic event, venous thromboembolic event of Grade 3 or higher per NCI CTCAE Version 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 3 months prior to the first dose; 9. Presence of any active autoimmune disease or history of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vasculothrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Use of replacement therapy (such as thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is permitted; 10. Within 4 weeks prior to the first dose, subjects who have undergone major surgery, experienced severe traumatic injury or fracture, or have poorly healed wounds; 11. Active systemic infection, including tuberculosis (clinical diagnosis includes clinical history, physical examination, imaging findings, and TB testing performed according to local medical practice), hepat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression Free Survival;Disease Control Rate;During of response;Overall Survival ;Adverse Event; | — |
Countries
China
Contacts
Public ContactWang Yan
Cancer Hospital of Chinese Academy of Medical Sciences
Outcome results
None listed