Triple-Negative Breast Cancer with Brain Metastases
Conditions
Interventions
Sponsors
Guangdong Provincial People's Hospital
Eligibility
Sex/Gender
Female
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Voluntary participation in this study, providing a signed and dated written informed consent form before any study-specific procedures, sampling, or analyses. 2. Female, aged >=18 years. 3. ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1. 4. Life expectancy >=3 months. 5. Histologically confirmed TNBC (HER2-/ER-/PR-negative) not amenable to curative surgery/radiotherapy. 6. B7-H3 positivity (IHC H-score >=100) confirmed by: - Prior test result OR - New testing of qualified tumor tissue/CSF sample. 7. Stable brain/leptomeningeal metastases per RANO-BM without need for: a) Immediate local therapy b) Increased corticosteroids c) New anticonvulsants. 8. >=1 evaluable intracranial lesion (per RANO-BM 2.0): - >=10 mm in 2 perpendicular diameters - Visible on >=2 contiguous MRI slices (thickness =4 mm). 9. Part 2 only: >=1 measurable extracranial lesion per RECIST v1.1. 10. Willing to provide FFPE blocks (6 unstained slides) or CSF for B7-H3 testing. 11. >=3 months since last cranial radiotherapy. 12. No CNS surgery/intrathecal therapy within 4 weeks (diagnostic LP allowed). 13. Laboratory requirements (within 7 days pre-dose): - Hematology: Platelets >=100×10?/L (>=50×10?/L if marrow involvement) ANC >=1.5×10?/L (>=1.0×10?/L if marrow involvement) Hemoglobin >=90 g/L Lymphocytes >=0.5×10?/L - Hepatic: Bilirubin =50 mL/min - Coagulation: INR/PT/aPTT <=1.5×ULN - Cardiac: QTcF <=450 ms (M) / <=470 ms (F). 14. Toxicity from prior therapy resolved to <=Grade 1 (alopecia excluded). 15. WOCBP must use effective contraception until 180 days post-treatment.
Exclusion criteria
Exclusion criteria: 1. Known hypersensitivity to the investigational product or its excipients. 2. Central nervous system metastases from hematologic malignancies (e.g., lymphoma, leukemia). 3. Metastases involving the brainstem or upper cervical cord (midbrain, pons, medulla, C1/C2 segments). 4. Significant mass effect with intracranial hypertension (e.g., severe headache, projectile vomiting, papilledema, impaired consciousness; or imaging findings: significant edema, midline shift >=1 cm, compressed cisterns). 5. Spinal cord compression (symptomatic or asymptomatic, radiologically confirmed). 6. Refractory chronic intracranial hypertension (e.g., daily mannitol >500 mL, dexamethasone >15 mg, methylprednisolone >80 mg, or equivalent corticosteroid doses). 7. Drug-refractory primary or secondary epilepsy/seizure disorders. 8. Single intracranial lesion >5 cm in maximum diameter or cumulative diameter >6 cm for multiple lesions. 9. Acute/chronic hydrocephalus. 10. CSF flow obstruction due to compartmentalization or gelatinous CSF from intracranial/intraspinal metastases. 11. Severe neurocognitive dysfunction per investigator assessment. 12. Participation in other investigational drug trials within 4 weeks prior to screening. 13. Prior treatment with B7-H3 antibodies, ADCs, or any cellular therapy. 14. History of other malignancies within 5 years (except cured cervical carcinoma in situ, papillary thyroid carcinoma, or basal cell skin cancer). 15. Active autoimmune disease, autoimmune history, or conditions requiring immunosuppressive therapy (exceptions: non-systemic skin disorders; resolved childhood asthma/allergies; stable hypothyroidism on hormone replacement). 16. Systemic corticosteroids (>=10 mg/day prednisone equivalent) or other immunosuppressive therapy. 17. Prior allogeneic tissue/solid organ transplantation. 18. Live vaccination within 2 weeks before cell therapy or planned during the study. 19. Active infections:HBV (unless controlled),HCV (unless RNA-negative),HIV, syphilis, EBV, or CMV viremia. 20. Active systemic infection or coagulopathy. 21. Grade >=3 thromboembolic events within 6 months or ongoing anticoagulation/thrombolysis. 22. Hereditary/acquired hemorrhagic disorders. 23. Clinically significant cardiovascular disease: NYHA Class >2 heart failure (past year), Unstable angina (past year), Myocardial infarction (past year), Malignant arrhythmias (excluding atrial fibrillation/paroxysmal SVT), Uncontrolled hypertension (SBP >140 mmHg or DBP >90 mmHg despite optimal therapy). 24. Active infection. 25. Active tuberculosis (confirmed by history/CT) or untreated latent TB within 1 year. 26. Pregnancy or lactation. 27. Contraindications to MRI. 28. Any condition deemed ineligible by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-Limiting Toxicity;Objective Response Rate;Recommended Phase 2 Dose; | — |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of Graft-versus-Host Disease;Incidence of CRS;Incidence of ICANS;Incidence of MT027 Cell Injection-related Adverse Events and Serious Adverse Events ;Disease Control Rate;Progression-Free Survival;Progression-Free Survival Rate;Overall Survival;Overall Survival Rate;AUC0-28d Cmax Tmax T1/2;Cmin,ss Cmax,ss Cav,ss DF AUC0-t Tmax,ss Rac;Maximum Tolerated Dose; | — |
Countries
China
Contacts
Public ContactNing Liao
Guangdong Provincial People's Hospital
Outcome results
None listed