The METAMAX Study: MT027 Allogeneic CAR-T for Brain Metastases From Advanced Solid Tumors

Ki vehet részt

• Age 18-75 years
• signed informed consent obtained before any study procedure
• Histologically/cytologically confirmed advanced solid tumor with brain metastases
• ≥1 measurable brain parenchymal lesion (≥5 mm on MRI)
• B7-H3 positive expression in tumor tissue by central IHC
• CNS disease progressed after, unsuitable for, or not requiring immediate standard local therapy (SRS/WBRT/surgery), per investigator and multidisciplinary review
• Previously received, intolerant to, or ineligible for any CNS-active targeted therapy for actionable driver alterations
• Extracranial disease stable ≥8 weeks and not requiring systemic therapy change; non-ADC chemotherapy discontinued ≥3 weeks before study treatment; Prior CNS local therapy permitted, provided the target lesion shows clear progression and does not overlap a previously treated SRS field (≥2-week interval)
• Treatment-related toxicities resolved to ≤Grade 1 or baseline (alopecia, ≤Grade 2 neuropathy, and specified lab values permitted)
• ECOG 0-2 and life expectancy ≥12 weeks
• Adequate organ and marrow function (ANC ≥1.5×10⁹/L, PLT ≥100×10⁹/L, Hgb ≥90 g/L, AST/ALT ≤3×ULN, TBili ≤1.5×ULN, Cr ≤1.5×ULN or CrCl ≥30 mL/min, INR/APTT ≤1.5×ULN, LVEF >50%, SpO₂ ≥95%)
• Effective contraception from screening through 120 days after last dose; negative pregnancy test within 72 hours before first dose (for WOCBP)

Ki nem vehet részt

• Active pulmonary tuberculosis within 1 year prior to study treatment
• Other investigational therapy within 4 weeks or 5 half-lives, whichever is longer
• Prior allogeneic transplant or CAR-T / other gene-modified cell therapy
• Systemic immunosuppression within 4 weeks, or corticosteroids >dexamethasone 2 mg/day (or equivalent) / not stabilized ≤2 mg/day for ≥7 days
• Live vaccine within 2 weeks before, or planned during, study treatment. Inability to safely undergo ICV / Ommaya reservoir procedures
• Major surgery, open biopsy, or significant trauma within 2 weeks (Ommaya placement excepted; wounds must be fully healed)
• CNS disease requiring urgent intervention (mass effect, herniation, hemorrhage, hydrocephalus, progressive neurologic symptoms); uncontrolled seizures or antiepileptic escalation within 4 weeks
• Active autoimmune disease requiring systemic treatment (type 1 DM, hypothyroidism on replacement, and non-systemic skin disorders permitted); Clinically significant uncontrolled cardiovascular, pulmonary, hepatic, renal, coagulation, or neurologic disease
• Active uncontrolled infection or HBV/HCV/HIV/syphilis
• Known hypersensitivity to any component of the study intervention
• Unlikely to comply with follow-up or protocol procedures, or any condition that, in the investigator's judgment, compromises safety or participation
• Target lesion >4 cm, unsafe location, or CNS tumor burden posing unacceptable risk
• Leptomeningeal metastasis
• VP shunt or other CSF diversion device