The GLIOMAX Study: MT027 Allogeneic CAR-T for Recurrent Glioma

Inclusion Criteria

• •1. Written informed consent must be obtained prior to any procedures that are not considered SOC
• •2. ≥ 18 years old and ≤ 70 years old on the day of signing informed consent, male or female
• •3. According to the WHO Classification of Tumors of the CNS (2021), definitely diagnosed recurrent or progressive GBM, WHO Grade 4, which must meet all 3 of the following criteria:
• •* According to the histological/molecular pathology, diagnosed with GBM WHO grade 4
• •* According to the histopathology or radiological imaging, confirmed disease progression or recurrence
• •* First recurrence after failure to the SOC therapy of newly diagnosed disease-Stupp regimen (which was surgery + standard RT + concurrent TMZ and adjuvant TMZ), or first recurrence after failure to the SOC therapy of newly diagnosed disease-Stupp regimen (which was surgery + standard RT + concurrent TMZ and adjuvant TMZ) and received Bevacizumab treatment
• •4. Participants with either unresectable lesions, or with resectable lesions who have undergone prior surgical resection, or with resectable lesions and no planned reoperation within 3 months after enrollment based on Investigator's judgment
• •5. Participants voluntarily provide the latest archival tumor or fresh biopsies FFPE samples (at least 8 consecutive non-stained sections) for B7H3 expression test by Immunohistochemistry (IHC), and the clinical pathology confirms positive B7H3 expression, defined as the proportion of 2+ and 3+ ≥ 20% (Reference refer to Appendix 13.1) or historical B7H3 positive expression within 12 months at the time of enrollment
• •6. Karnofsky Performance Status (KPS) score ≥ 60
• •7. Life expectancy of ≥ 12 weeks
• •8. Adequate organ and marrow functions as defined below: (blood transfusion, blood component transfusion, or hematopoietic stimulating factors within 7 days prior to the first dose is not allowed)
• •1. Hematological: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L, and hemoglobin ≥ 90 g/L
• •2. Hepatic: ALT and AST ≤ 3 × ULN, total bilirubin ≤ 1.5 × ULN
• •3. Renal: Serum creatinine (Cr) ≤ 1.5 × ULN, or calculated Cr clearance ≥ 30.0 mL/min using Cockcroft-Gault formula
• •4. Coagulation: International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (participant is receiving anticoagulant therapy in which case the APTT and INR must be within the therapeutic range of intended use for the anticoagulant)
• •5. Cardiac: Left ventricular ejection fraction (LVEF) \> 50%
• •6. Oxygen saturation ≥ 95% on room air
• •9. Has adequate treatment washout period before IP treatment, defined as:
• •Major surgery : ≥ 2 weeks§; Ommaya reservoir placement surgery was excluded Radiation therapy : ≥ 12 weeks (unless the progression is clearly outside the radiation field (e.g., beyond the high-dose region or 80% isodose line) or there is pathologic confirmation of disease progression) Chemotherapy :≥ 23 days for TMZ ; ≥ 6 weeks for Nitrosoureas or Mitomycin C (such as: Carmustine, Lomustine and so on) Biologic agents\* (such as: PD1/PD-L1 antibodies) : ≥ 4 weeks Small molecule targeted drugs (TKIs such as Regorafenib and Anlotinib) : ≥ 3 weeks or 5 half-lives (including toxic metabolites), whichever is longer Other antitumor therapies :≥ 4 weeks
• •§Any surgery incisions or wounds must be completely healed
• •\*Not including Bevacizumab
• •10. Intracranial hemorrhage Grade ≤ 1 (per NCI-CTCAE v5.0), and toxicity from previous systemic treatment returns to ≤ Grade 1 or baseline before the first CAR-T dose (except alopecia)
• •11. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time of the pre-study visit, through the course of the study and for 120 days after the last dose of study medication
• •* Female patients of childbearing potential should have a negative serum pregnancy within 72 hours prior to receiving the first dose of study medication
• •* Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year
• •* Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately