Brain, leptomeningeal, and spinal cord metastases from solid tumors
Conditions
Interventions
MT027 group:MT027 cell injection
Sponsors
Cancer Hospital, Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Volunteer to participate in this study and provide a signed and dated informed consent form before any specific research procedures, sampling, or analysis are conducted; 2. Age >= 18 years, gender not specified; 3. Diagnosed with malignant tumor by pathology and/or histopathology (and provide complete pathology report information), confirmed by biopsy, cytology, imaging examination, etc., or previously confirmed with brain, cerebrospinal fluid, or spinal cord metastasis, including lung cancer, breast cancer, colorectal cancer, melanoma, renal cell carcinoma, etc. Other solid tumors with CNS metastasis without standard treatment may also be considered for enrollment; 4. Intracranial metastatic lesions must meet the following characteristics: 1) Single/localized (3 lesions) intracranial metastatic lesions that cannot be completely resected by craniotomy; or meningeal metastasis, or spinal cord metastasis that cannot be operated on; 2) Intracranial lesions that have received standard treatment, including whole-brain radiotherapy/stereotactic radiotherapy (WBRT/SRS) and have progressed after standard treatment, and are not suitable for further radiotherapy; 5. Extracranial lesions (including primary tumor sites and systemic multi-organ/system metastatic lesions) must meet the following characteristics: 1) Failure of standard-of-care (SOC) standard treatment for primary tumor sites and systemic metastatic lesions, with no current standard therapy, may be enrolled in this study; 2) Extracranial lesions controlled stable under current systemic treatment regimen, with intracranial progression expected during the study treatment period, and without change of treatment plan expected, may also be enrolled in this study; 3) Based on the investigator's judgment, changing the systemic treatment regimen during the study treatment period would not adversely affect the study treatment, may also be enrolled in this study; 6. For patients with brain/spinal cord parenchymal metastasis, enhanced MRI must show at least one measurable lesion (according to iRANO criteria); for patients with only; 7. The subjects voluntarily provided the latest FFPE tissue or pathological section (6 consecutive white slices) or cerebrospinal fluid tumor cells for B7-H3 expression detection, and the cytological detection of B7-H3 in the tumor tissue/cerebrospinal fluid was positive; 8. =3 months from the last intracranial/spinal radiotherapy; 9. No surgical treatment or subarachnoid drug administration for intracranial or intraspinal lesions was performed within 1 month before signing the informed consent (except diagnostic puncture such as lumbar puncture); 10. Expected survival >=3 months; 11. KPS (Karnofsky) score >=70 points. 12. Laboratory tests during the screening period meet the following criteria: (1)Blood routine (within 14 days) : 1) White blood cell (WBC) >=3.0×109 /L; 2)neutrophil absolute count (ANC) >=1.5×109 /L; 3) lymphocyte >=0.8×109 /L; 4)Platelet count (PLT) >=100×109 /L; 5) Hemoglobin (HGB) >=90 g/L (blood transfusion and erythropoietic agents permitted). If there is active bleeding or other persistent conditions that result in increased destruction or impaired production of red blood cells, repeated transfusions or red blood cell therapy may be required, and patients must discuss their eligibility with co-organizers on a case-by-case basis prior to enrollment.) ; (2)Liver function (within 7 days) : 1) Total bilirubin (TIBC) <= 1.5
Exclusion criteria
Exclusion criteria: 1. Known allergy to the investigational drug or its excipients; 2. Hematological system tumors (such as lymphoma, leukemia, etc.) with central nervous system metastasis; 3. Patients with brain stem and high cervical pulp metastasis, including midbrain, pontine, medulla oblongata and C1/2 cervical pulp; 4. Intracranial lesions had obvious space-occupying effect, and there were signs of high cranial pressure (such as severe headache, ejection vomiting, visual papilledema, disturbance of consciousness, or obvious edema indicated by imaging, midline migration =1cm, and peripheral cisterna pressure signs such as suprabellar cisterna, quadristoid cisterna, interfoot cisterna, and annular cisterna); 5. There is drug-refractory chronic cranial hypertension (such as daily use of mannitol >500ml or dexamethasone >15mg or methylprednisolone > 80mg or equivalent doses of other hormones); 6. Patients with primary or secondary epilepsy/epileptic syndrome that is difficult to control with drugs; 7. The largest diameter of a single intracranial tumor lesion >5cm, or the largest diameter of multiple intracranial lesions >6cm; 8. Acute/chronic hydrocephalus; 9. Cerebrospinal fluid (CSF) flow obstruction caused by intracranial/spinal canal metastasis, such as cerebrospinal fluid separation and jelly-like cerebrospinal fluid, cannot be removed after treatment; 10. Patients with severe neurocognitive dysfunction judged by researchers; 11. Is receiving systemic steroid therapy (other than physiological hormone replacement therapy) or any other form of immunosuppressive therapy within 1 week prior to the first trial treatment; 12. Participated in other drug clinical trials within 4 weeks prior to screening; 13. Previous B7H3 antibody or ADC or cell therapy; 14. Patients with other primary malignancies (except cured cervical carcinoma in situ, thyroid papillary carcinoma, and skin basal cell carcinoma); 15. People with severe autoimmune diseases; 16. Subjects who have previously received allogeneic tissue/solid organ transplants; 17. Subjects who received live vaccine within 2 weeks prior to the first cell therapy or who plan to receive live vaccine during the study period; 18. Persons with active hepatitis B virus; Or infected with hepatitis C virus (defined as HCV antibody positive if HCV-RNA is below the lower limit of detection); Or infected with human immunodeficiency virus (defined as HIV-positive); Or treponema pallidum antibody positive; Or Epstein-Barr virus (EBV), cytomegalovirus (CMV) active infection; 19. Patients with active systemic infections, coagulation disorders and other major diseases; 20. Severe heart, lung, liver and kidney insufficiency; Heart function: Level 3 or above according to New York Heart Association (NYHA) standards; Liver function: Child-Puge grade C or above; Renal function: chronic kidney disease (CKD) stage 4 or above; Renal insufficiency stage III or above; Lung function: Symptoms of severe respiratory failure, involving other organs; 21. Pregnant and lactating women; 22. The investigator considers that there are any clinical or laboratory abnormalities or other reasons to be unsuitable for participating in this clinical study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-Limiting Toxicity; | — |
Secondary
| Measure | Time frame |
|---|---|
| Chimeric Antigen Receptor copy number;Interleukin-2;Interleukin-4;Interleukin-6;Interleukin-8;Interleukin-10;Interferon-?;Tumor necrosis factor-a; | — |
Countries
China
Contacts
Public ContactNing Li
Cancer Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed