Can a targeted drug plus brain radiation shrink lung cancer brain tumors?

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Age ≥ 18 years, any sex. * Histologically or cytologically confirmed advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) (per AJCC 8th edition TNM staging). * Radiologically confirmed brain metastases and considered suitable for brain radiotherapy by the investigator. * Presence of EGFR-sensitizing mutations, including exon 19 deletion or exon 21 L858R point mutation. * Prior treatment with a third-generation EGFR-TKI as first-line therapy with documented intracranial progression, regardless of extracranial progression status. * Any number of brain metastases is allowed; symptomatic brain metastases are permitted. * At least one measurable intracranial target lesion per RECIST 1.1 that has not been previously irradiated or surgically treated; lesions ≥5 mm in diameter are acceptable as target lesions. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Life expectancy of at least 3 months. * Adequate organ and bone marrow function (without transfusion, thrombopoietin, or colony-stimulating factor support within 2 weeks before the first dose), defined as: * Hematology: Absolute neutrophil count ≥1.5×10⁹/L; platelets ≥100×10⁹/L; hemoglobin ≥100 g/L. * Hepatic: AST, ALT, and ALP ≤2.5× upper limit of normal (ULN); total bilirubin ≤1.5×ULN; albumin ≥30 g/L. For subjects with baseline liver metastases, ALT and AST ≤5×ULN and total bilirubin ≤3×ULN are allowed. * Renal: Serum creatinine ≤1.5×ULN or calculated creatinine clearance ≥50 mL/min (Cockcroft-Gault formula). * Coagulation: INR, APTT, and PT ≤1.5×ULN. * Female subjects of childbearing potential and male subjects with partners of childbearing potential must agree to use effective medical contraception from signing of informed consent through 6 months after the last dose. * Willing and able to provide written informed consent and comply with study follow-up. Exclusion Criteria: * Histological or cytological evidence of small cell lung cancer, neuroendocrine carcinoma, carcinosarcoma, or squamous cell carcinoma components. * Prior systemic anti-tumor therapy for locally advanced or metastatic NSCLC other than third-generation EGFR-TKI (first-line EGFR-TKI combined with chemotherapy is allowed). * Prior treatment with any TROP2-targeted therapy or any drug containing a topoisomerase I inhibitor, including antibody-drug conjugates (ADCs) (including in the adjuvant/neoadjuvant setting). * Known leptomeningeal metastases, brainstem metastases, spinal cord metastases, or spinal cord compression. * Prior radiotherapy to the brain. * Other malignancy within 3 years before the first dose, except for curatively treated tumors such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix. * Presence of any of the following cardiovascular or cerebrovascular diseases or risk factors: 1. Myocardial infarction, unstable angina, acute or persistent myocardial ischemia, New York Heart Association (NYHA) Class 3 or 4 heart failure, symptomatic or uncontrolled severe arrhythmia, cerebrovascular accident, transient ischemic attack, or other severe cardiovascular/cerebrovascular events within 6 months before first dose. 2. History of myocarditis, primary cardiomyopathy, or specific cardiomyopathy. 3. Any deep vein thrombosis (unless stable on low-molecular-weight heparin or equivalent therapy for ≥2 weeks), peripheral arterial thromboembolic event, pulmonary embolism, or other severe thromboembolic event within 3 months before first dose. 4. Aortic aneurysm, aortic dissection, or other major vascular disease that may be life-threatening or requires surgery within 6 months before first dose. * Uncontrolled systemic diseases per investigator judgment: 1. Poorly controlled diabetes (fasting blood glucose ≥10 mmol/L on two consecutive measurements). 2. Poorly controlled hypertension (systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg). 3. Clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring repeated drainage (\>1 time/week). * History of (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonitis that required steroids, current ILD/non-infectious pneumonitis, or suspected ILD/non-infectious pneumonitis that cannot be excluded by imaging at screening. * Documented severe dry eye syndrome, severe meibomian gland disease, and/or blepharitis, or history of severe corneal disease that prevents/delays corneal healing. * Clinically severe pulmonary impairment due to concurrent lung disease, including but not limited to any underlying lung disease (e.g., severe asthma within 3 months before first dose, severe COPD, restrictive lung disease) or any autoimmune, connective tissue, or inflammatory disease that may involve the lungs (e.g., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis), or prior total pneumonectomy. * Active chronic inflammatory bowel disease, gastrointestinal obstruction, severe ulcer, gastrointestinal perforation, intra-abdominal abscess, or acute gastrointestinal bleeding. * Active gastrointestinal disease or other conditions that significantly affect absorption, distribution, metabolism, or excretion of oral study drugs (however, this study uses IV administration; still included per protocol) - e.g., refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow capsules, or prior major bowel resection. * Risk of esophagotracheal fistula or esophagopleural fistula, or tumor invasion/compression of vital organs or vessels (e.g., heart, esophagus, superior vena cava) with associated symptoms (e.g., superior vena cava syndrome). * Prior anti-tumor therapy toxicity not recovered to ≤ grade 1 (per NCI CTCAE v5.0) or to the level specified in the eligibility criteria (except alopecia, fatigue, or other low-risk toxicities per investigator judgment). * Active autoimmune disease requiring systemic treatment within the past 2 years (e.g., disease-modifying agents, immunosuppressants, systemic corticosteroids \>10 mg/day prednisone or equivalent). Hormone replacement therapy (e.g., thyroid hormone, insulin, or physiologic corticosteroid replacement for adrenal/pituitary insufficiency) is not considered systemic treatment. Subjects receiving systemic corticosteroids \>10 mg/day prednisone or other immunosuppressants within 2 weeks before first dose are excluded. * Severe infection within 4 weeks before first dose (including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia), or active infection requiring systemic anti-infective therapy within 2 weeks before first dose. * Known active tuberculosis. Subjects with suspected active tuberculosis must be ruled out by clinical examination. * Active hepatitis B (HBsAg positive with HBV-DNA ≥500 IU/mL or above the lower limit of detection, whichever is higher) or active hepatitis C (HCV antibody positive with HCV-RNA above the lower limit of detection), or co-infection with HBV and HCV. * Positive HIV test or history of AIDS; known active syphilis infection. * History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation. * Major surgery within 4 weeks before first dose, or planned major surgery during the study. * Known hypersensitivity to the study drug or any of its components (including polysorbate-20), or history of severe hypersensitivity reactions to other biologics. * Receipt of non-specific immunomodulatory therapy (including but not limited to interferon, IL-2) or Chinese patent medicines with approved anti-tumor indications within 2 weeks before first dose. * Receipt of strong CYP3A4 inhibitors or inducers within 7 days before first dose, or need for continued use of these drugs during the study. * Vaccination with live vaccine within 30 days before first dose, or planned live vaccination during the study. * Rapid deterioration of clinical condition during the screening period (e.g., significant change in performance status). * Pregnancy or breastfeeding. * Any other condition that, in the investigator's opinion, would interfere with the evaluation of the study drug, subject safety, or interpretation of study results, or that makes the subject unsuitable for participation.