Driver Gene-negative Lung Cancer Complicated by Brain and/or Leptomeningeal Metastases
Conditions
Interventions
Sponsors
Guangdong Provincial People's Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Voluntarily participate in this study and provide signed and dated written informed consent before any study-specific procedures, sampling, or analyses; 2. Age >=18 years, any gender; 3. Have a confirmed pathological and/or histological diagnosis of lung cancer (excluding pulmonary lymphoepithelioma-like carcinoma, with complete pathological report information provided) and have confirmed or previously confirmed lung cancer brain/leptomeningeal metastasis via biopsy, cytology, imaging, etc.; 4. Intracranial metastases must satisfy condition 1) + 2) or condition 1) + 3): 1) Patients with solitary/limited (3 lesions) intracranial metastases not amenable to complete resection via craniotomy; or with leptomeningeal metastasis, or spinal cord metastasis not suitable for surgery; 2) Intracranial lesions with progression after standard treatment (e.g., whole-brain radiotherapy/stereotactic radiosurgery [WBRT/SRS]); 3) Subjects who refuse WBRT/SRS. 5. Extracranial lesions (including primary lesion and systemic multi-organ/system metastases) must meet the following characteristics: 1) Failure of standard of care (SOC) treatment for the primary lesion and systemic metastatic lesions; 2) Extracranial lesions are stable under systemic therapy. 6. For patients with brain parenchymal metastases: at least one measurable lesion on contrast-enhanced MRI (according to iRANO criteria); for patients with leptomeningeal lesions only: may be considered for enrollment if, in the investigator's judgment, they are likely to benefit from the study treatment (efficacy will be assessed per RANO-LM criteria). 7. Subjects voluntarily provide the most recent FFPE tissue or pathological sections (6 consecutive unstained slides) or cerebrospinal fluid tumor cells for central laboratory B7-H3 expression testing, with B7-H3 positive expression in tumor tissue/CSF cytology (positivity defined as H-Score >=100 in tumor tissue or sections). 8. At least 3 months since the last intracranial/intrathecal radiotherapy. 9. No surgical treatment or intrathecal administration (excluding diagnostic lumbar puncture, etc.) for intracranial/intraspinal lesions within 1 month prior to signing the informed consent. 10. Expected survival >=3 months. 11. Karnofsky Performance Status (KPS) score >=70. 12. Laboratory tests during the screening period meet the following criteria: **Hematology (within 14 days):** • White Blood Cell (WBC) count >=3.0 × 10?/L; • Absolute Neutrophil Count (ANC) >=1.5 × 10?/L; • Lymphocytes >=0.8 × 10?/L; • Platelet count (PLT) >=100 × 10?/L; • Hemoglobin (HGB) >=90 g/L (transfusion and use of erythropoiesis-stimulating agents are permitted. If active bleeding or other persistent conditions lead to increased red cell destruction or impaired production, requiring repeated transfusions or red cell therapy, the patient's eligibility must be discussed with the Sponsor on a case-by-case basis prior to enrollment.); **Liver Function (within 7 days):** • Total Bilirubin (TBil) =30 mL/min (estimated by Cockcroft-Gault formula); **Coagulation (within 7 days):** • International Normalized Ratio (INR) or Prothrom
Exclusion criteria
Exclusion criteria: 1. Known allergy/hypersensitivity to the investigational product. 2. Pulmonary lymphoepithelioma-like carcinoma positive for Epstein-Barr virus (EBV). 3. Presence of brainstem or high cervical spinal cord metastases, including midbrain, pons, medulla oblongata, and C1/C2 spinal segments. 4. Intracranial lesions with significant mass effect and signs of elevated intracranial pressure (e.g., severe headache, projectile vomiting, papilledema, impaired consciousness, or imaging findings indicating significant edema, midline shift >=1 cm, effacement of perimesencephalic cisterns such as the suprasellar, quadrigeminal, interpeduncular, or ambient cisterns). 5. Drug-refractory chronic intracranial hypertension (e.g., daily use of mannitol >500 ml, or dexamethasone >15 mg, or methylprednisolone >80 mg, or equivalent doses of other corticosteroids). 6. Primary or secondary epilepsy/epileptic syndrome refractory to medical control. 7. Largest diameter of any single intracranial tumor lesion >5 cm, or cumulative diameter of multiple intracranial lesions >6 cm. 8. Presence of acute/chronic hydrocephalus. 9. Intracranial/intraspinal metastatic lesions causing compartmentalization of cerebrospinal fluid (CSF), "jelly-like" CSF, or obstruction of CSF flow that cannot be resolved with treatment. 10. Significant neurocognitive dysfunction, as judged by the investigator. 11. Systemic steroid therapy (excluding physiologic hormone replacement) or any other form of immunosuppressive therapy within 1 week prior to the first study treatment. 12. Participation in another investigational drug trial within 4 weeks prior to screening. 13. Prior treatment with any B7-H3 antibody, Antibody-Drug Conjugate (ADC), or cell therapy. 14. Concurrent other primary malignancy (except carcinoma *in situ* of the cervix, papillary thyroid carcinoma, and basal cell carcinoma of the skin that have been cured). 15. Severe autoimmune disease. 16. Patients with a history of allogeneic tissue/solid organ transplantation. 17. Administration of a live vaccine within 2 weeks prior to the first cell therapy or planning to receive a live vaccine during the study period. 18. Active hepatitis B virus (HBV) infection; or hepatitis C virus (HCV) infection (defined as HCV antibody positive, although enrollment may be allowed if HCV-RNA is below the lower limit of detection); or human immunodeficiency virus (HIV) infection (defined as HIV antibody positive); or positive *Treponema pallidum* antibody; or active infection with Epstein-Barr virus (EBV) or Cytomegalovirus (CMV). 19. Major diseases such as active systemic infection or coagulation disorders. 20. Severe cardiac, pulmonary, hepatic, or renal insufficiency: * Cardiac function: New York Heart Association (NYHA) Class III or higher. * Hepatic function: Child-Pugh Class C or higher. * Renal function: Chronic Kidney Disease (CKD) Stage 4 or higher; or Stage III or higher renal insufficiency. * Pulmonary function: Symptoms of severe respiratory failure affecting other organs. 21. Pregnant or lactating women. 22. Patients unable to tolerate cranial MRI examination. 23. Any other clinical or laboratory abnormality or reason that, in the opinion of the investigator, makes the patient unsuitable for participation in this clinical study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Dose-Limiting Toxicity;Objective Response Rate;Incidence of ICANS; | — |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of Graft-versus-Host Disease;Incidence of CRS;Incidence of MT027 Cell Injection-related Adverse Events and Serious Adverse Events ;Duration of Response;Disease Control Rate;Progression-Free Survival;Progression-Free Survival Rate;OS;OSR;AUC0-28d Cmax Tmax T1/2;Cmin,ss Cmax,ss Cav,ss DF AUC0-t Tmax,ss Rac;Maximum Tolerated Dose;Recommended Phase 2 Dose; | — |
Countries
China
Contacts
Public ContactWenzhao Zhong
Guangdong Provincial People's Hospital
Outcome results
None listed