FDA Clears Phase 2 Trial of B7-H3 CAR T MT027 for Brain Metastases

The FDA has allowed the launch of a phase 2 study of MT027, an allogeneic chimeric antigen receptor (CAR) T-cell therapy directed at B7-H3, in patients with brain metastases arising from lung or breast cancer.¹

This marks the second FDA-cleared phase 2 program for MT027 after a trial in recurrent glioblastoma (GLIOMAX-101; NCT07386002). The clearance follows early results from a phase 1 investigator-initiated trial (ChiCTR2500107346) presented at the International Association for the Study of Lung Cancer 2026 World Conference on Lung Cancer (WCLC).

“Receiving FDA clearance for two consecutive phase 2 studies of MT027 marks a pivotal step built on our sustained work in intracranial solid tumors,” management of T-MAXIMUM, developer of MT027, stated in a news release.

Background and Clinical Development

MT027 is an off-the-shelf product made with CRISPR-based editing that knocks out TRAC and HLA class I, which is intended to reduce the risks of graft-vs-host-disease (GVHD) and rejection by the host. The company stated the gene-editing process uses no viral vectors, that it may offer advantages in safety, batch consistency, and cost compared with lentiviral manufacturing, and that the process was finalized before phase 2 development began.

T-MAXIMUM has also investigated its allogeneic CAR T-cell platform in glioma through MT026, a product built with the same TRAC and HLA class I knockout approach but directed at IL-13Rα2 rather than B7-H3. In a single-center phase 1 investigator-initiated trial (ChiCTR2000028801) published in Nature Communications, 1 of 5 patients with high-grade recurrent glioma had a complete response, 3 had partial responses, and 1 had stable disease, with a median response duration of 3.8 months.² Median overall survival from the first infusion was 8.3 months, and no adverse events (AEs) of grade 3 or higher occurred. Enrollment stopped at 5 of 12 planned patients because of operational disruptions related to COVID-19.

Phase 1 Results Presented at WCLC

The phase 1 study of MT027 presented at WCLC, led by investigators at Sanbo Brain Hospital of Capital Medical University in Fuzhou, China, enrolled patients with lung cancer brain metastases whose disease had progressed after standard therapies and who had no further guideline-recommended options.¹ Cells are delivered into the central nervous system by intracerebroventricular or lumbar cistern injection. The dose-escalation design calls for 9 patients across 2 dose cohorts, and enrollment is continuing to establish a recommended phase 2 dose.

Of 5 heavily pretreated patients with refractory lung cancer brain metastases, 3 had measurable disease; 1 had a partial response with approximately 80% tumor shrinkage, and 2 had stable disease. Among the 2 patients with stable disease, 1 had a 46% reduction in tumor size and remained progression free for more than 8 months.^1,3 No drug-related AEs of grade 3 or higher and no GVHD were reported. AEs were mostly grade 1 or 2 immune-inflammatory reactions, which the investigators attributed to CAR T-cell activity in the central nervous system.

Brain Cancer Phase 2 Trial Planned

The FDA has granted MT027 orphan drug designation in high-grade glioma and fast track designation for recurrent or progressive glioblastoma.¹ The planned trial in patients with brain cancers will enroll patients with recurrent or progressive WHO grade 4 IDH-wildtype glioblastoma with a target enrollment of 40 patients, the first 6 of which will be the safety run-in cohort. Patients will receive injections on days 1 and 15 of each 28-day cycle until intolerable toxicity, disease progression, study withdrawal, or death.⁴

“Going forward, we will continue to rigorously evaluate the product’s safety and potential clinical value through well-designed clinical studies, steadily advancing product supply, clinical execution, and the generation of key data, as we explore new possibilities for patients who lack effective treatment options,” T-MAXIMUM management stated in the news release.¹

REFERENCES

1. T-MAXIMUM’s B7-H3-Targeted Allogeneic CAR-T MT027 Receives FDA Clearance for Phase 2 Study in Brain Metastases from Lung and Breast Cancer. News release. T-MAXIMUM Pharmaceutical. October 12, 2026. Accessed October 12, 2026. https://tinyurl.com/mrjpasf6

2. Li X, Shang X, Liu J, et al. Intrathecal CRISPR-edited allogeneic IL13Rα2 CAR T cells for recurrent high-grade glioma: preclinical characterization and phase I trial. Nat Commun. 2026;17:1362. doi:10.1038/s41467-025-68112-6

3. Lin Z, Shang X. B7-H3 universal CAR-T (MT027) for refractory lung cancer brain metastases: preliminary phase I IIT results. Presented at: IASLC 2026 World Conference on Lung Cancer; September 12-15, 2026; Seoul, Republic of Korea. Abstract P3.124.

4. The GLIOMAX Study: MT027 Allogeneic CAR-T for Recurrent Glioma (GLIOMAX-101). ClinicalTrials.gov. Updated September 29, 2026. Accessed October 12, 2026. https://clinicaltrials.gov/study/NCT07386002