lung cancer with brain metastases
Conditions
Interventions
Treatment group:Sacituzumab tirumotecan (Sac-TMT) plus bevacizumab
Sponsors
Sun Yat-sen University Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Age >= 18 when signing the informed consent form, regardless of gender; 2.Histologically or cytologically confirmed nonsquamous NSCLC with EGFR-sensitive mutation (exon 19 deletion or exon 21 L858R mutation). 3.Progression on or after 3rd-generation EGFR-TKI (change to the third-generation EGFR-TKIs after receiving 1st or 2nd generations of TKI, or to use the third-generation TKI in the first line are all allowed). 4.Brain parenchymal metastases confirmed by cranial MRI, including asymptomatic BM or those with symptoms controlled after local treatment and/or dehydration therapy, should maintain a clinically stable state (no longer requiring glucocorticoids or anticonvulsants) for at least 2 weeks before the first dose. 5.According to mRECIST 1.1, the subject must have at least one accurately measurable intracranial target lesion that has not been previously treated with local therapies such as radiation therapy or surgery. Brain metastatic lesions with a diameter of >= 5 mm are permitted to be designated as target lesions. 6.ECOG PS 0-1. 7.Estimated life expectancy of 12 weeks or more. 8.Adequate organ function.Patients who have not received transfusions, recombinant human thrombopoietin, or colony-stimulating factor treatment within 2 weeks prior to the first administration are defined as follows: a) Hematology: Absolute neutrophil count (NEUT#) >= 1.5 × 10?/L; Platelet count (PLT) >= 100 × 10?/L; Hemoglobin >= 90 g/L; b) Liver function: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 30 g/L; For subjects with baseline liver metastases, ALT and AST = 50 ml/min (calculated using the standard Cockcroft-Gault formula); d) Coagulation function: International normalized ratio (INR), activated partial thromboplastin time (APTT), and prothrombin time (PT) <= 1.5 × ULN. 9.Female subjects of childbearing potential and male subjects whose partners are of childbearing potential must agree to use effective medical contraceptive measures from the time of signing the informed consent form until 6 months after the last dose. 10.The subject voluntarily participates in this study, signs the informed consent form, and is able to comply with the study visits and related procedures as specified in the protocol. 11.There must be medical record documentation showing evidence of previous EGFR mutation test results (a known EGFR mutation sensitive to EGFR-TKI [Ex19del, L858R], which can exist alone or together with other EGFR mutations).
Exclusion criteria
Exclusion criteria: 1.Histologically or cytologically confirmed tumor with components of small cell lung cancer, neuroendocrine carcinoma, carcinosarcoma, or squamous cell carcinoma; 2.Patients with spinal cord compression or those assessed by the investigator as having extensive meningeal metastasis; 3.Previous whole-brain radiotherapy for brain metastases; 4.Subjects who have previously received chemotherapy, TROP2-targeted therapy, or any drug therapy containing topoisomerase I inhibitors, including antibody-drug conjugate (ADC) therapy (including in the context of adjuvant or neoadjuvant therapy); 5.Tumor invading or surrounding important surrounding organs and blood vessels (such as the heart, esophagus, superior vena cava, etc.), or with obvious necrosis, cavitation, or at risk of developing esophagotracheal fistula or esophagopleural fistula; 6.A history of bleeding tendency or coagulation disorder and/or clinically significant bleeding symptoms or risks within 4 weeks before the first dose; 7.Use of aspirin (> 325 mg/day) or treatment with dipyridamole or clopidogrel within 2 weeks before the first dose; 8.Use of full-dose oral or intravenous anticoagulants or thrombolytics within 2 weeks before the first dose; 9.Biopsy or other minor surgeries (excluding placement of vascular access devices) within 7 days before the first dose; 10.Presence of non-healing wounds or untreated fractures (excluding old fractures and other fractures that do not require treatment); 11.History of other malignant tumors within 3 years before the first dose (except tumors cured by local treatment, such as cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, cervical carcinoma in situ, etc.); 12.Presence of any of the following cardiovascular and cerebrovascular diseases or risk factors:a) Myocardial infarction, unstable angina pectoris, acute or persistent myocardial ischemia, grade 3 or 4 heart failure (according to the New York Heart Association (NYHA) classification), symptomatic or poorly controlled severe arrhythmia, cerebrovascular accident, transient ischemic attack, or other severe cardiovascular and cerebrovascular diseases within 6 months before the first dose; b) Previous history of myocardial diseases such as myocarditis, primary cardiomyopathy, or specific cardiomyopathy; c) Any deep vein thrombosis within 3 months before the first dose (subjects with stable condition after treatment with low-molecular-weight heparin or drugs with similar effects for = 2 weeks are permitted to enroll), peripheral arterial thromboembolic events, pulmonary embolism, or other severe thromboembolic events; d) Presence of major vascular diseases that may be life-threatening or require surgery within 6 months before the first dose, such as aortic aneurysm or aortic dissecting aneurysm; 13.Uncontrolled systemic diseases as judged by the investigator:; 14.History of (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonia requiring steroid treatment, current ILD or non-infectious pneumonia, or suspected ILD or non-infectious pneumonia at screening that cannot be excluded by imaging examinations; 15.Documented history of severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or severe corneal diseases that may impede/delay corneal healing; 16.Clinically severe lung damage caused by concurrent pulmonary diseases, including but not limited to any underlying lung diseases (such as severe asthma, severe chronic obstructive pulmonary di
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Intracranial objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Systemic progression-free survival;Overall survival;Systemic objective response rate;Intracranial progression-free survival;Safety; | — |
Countries
China
Contacts
Public ContactLikun Chen
Sun Yat-sen University Cancer Center (Sun Yat-sen University Affiliated Cancer Hospital, Sun Yat-sen University Cancer Research Institute)
Outcome results
None listed