Starting soon
Phase 2
The METAMAX Study: MT027 Allogeneic CAR-T for Brain Metastases From Advanced Solid Tumors
Condition(s) studied
Brain Metastases From Solid Tumors
Investigational drug(s) / intervention(s)
Intracerebroventricular injection of MT027 UCAR-T Cell targeting B7H3
Intracerebroventricular injection of MT027 UCAR-T Cell targeting B7H3: MT027 will be injected intracerebroventricularly at a dose of 3×10\^7 cells on Day 1 \& Day 15 of each 28-day treatment cycle.
Study summary
This is a prospective, open-label, multicenter, single arm Phase II trial to evaluate the safety, tolerability, intracranial efficacy, pharmacokinetics, and pharmacodynamics of MT027 administered ICV in patients with B7-H3-positive brain metastases from advanced solid tumors.
The trial consists of two sequential stages: a safety run-in stage followed by a dose expansion stage. Approximately 40 participants are planned for enrollment, including approximately 3 to 6 participants in the safety run in stage and 34 participants in the dose expansion stage. The final number of participants enrolled may vary depending on the safety findings observed during the safety run-in stage.
Approximately 3 to 6 eligible participants from the primary target population will receive MT027 3×107 CAR+ T cells via ICV injection on Days 1 and 15 of each 28-day cycle. DLTs will be assessed during a 28-day DLT observation period following the first dose.
Following SRC confirmation of acceptable safety during the safety run-in stage, an additional 34 participants will be enrolled to evaluate the intracranial efficacy of MT027 dosed at 3×107 CAR+ T cells.
Eligibility
Inclusion Criteria
* 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).
Exclusion Criteria
* CNS disease requiring urgent intervention (mass effect, herniation, hemorrhage, hydrocephalus, progressive neurologic symptoms); uncontrolled seizures or antiepileptic escalation within 4 weeks.
* Target lesion \>4 cm, unsafe location, or CNS tumor burden posing unacceptable risk.
* Leptomeningeal metastasis.
* 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.
* 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.
* VP shunt or other CSF diversion device.
* Major surgery, open biopsy, or significant trauma within 2 weeks (Ommaya placement excepted; wounds must be fully healed).
* 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.
Primary outcome measure(s)
- Incidence rate of Dose-limiting toxicity (DLT) — up to 28 days
Incidence rate of Dose-limiting toxicity (DLT) after treatment in the safety run-in stage
- Intracranial progression-free survival at 6 months (iPFS6) — up to 6 months
defined as the time from treatment initiation to disease progression in central nervous system (CNS), or death, whichever occurs first, or considered censored at the end of follow-up.
Trial sites (2)
| Facility | City | Region | Status |
|---|
| Delta Hy Research |
Houston |
Texas |
|
| Chang Gung Memorial Hospital, Linkou |
Taoyuan |
Taoyuan |
|
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