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IL13Rα2 Universal CAR T Therapy Shows Antitumor Activity in Recurrent Glioma

MT026 had an overall response rate of 83.3% in a first-in-human, investigator-initiated trial.

MT026, an IL13Rα2-targeted universal chimeric antigen receptor T-cell (UCAR-T cell) therapy, was well-tolerated and demonstrated anti-tumor activity in recurrent glioma.

These data, from a single-center, first-in-human, investigator-initiated trial in China, were presented at the European Society for Medical Oncology (ESMO) Congress 2022, taking place September 9-13 in Paris, France, by Yulun Huang, MD, professor, department of neurosurgery, Dushu Lake Hospital and Soochow University, Suzhou, China.

“Glioblastoma is the most common intracranial malignant tumors, which is difficult to treat and has poor prognosis,” Huang and colleagues wrote.

Huang and colleagues treated 6 patients with recurrent glioma with MT026 as of July 2022. These patients had a median age of 52 years and 4 were female. They mostly had medium IL13Rα2 expression.

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Cells expanded well and persisted for over 30 days. Investigators noted an expansion-correlated response in study participants, all but 1 of which responded. Response also seemed correlated to IL13Rα2 tumor expression.

“Use of autologous T cell immunotherapy for treatment of high-grade glioma… is limited. Off-the-shelf allogeneic universal CAR-T cells have unique advantages and clinical potential for those tumors which tissues are hard to collect and progress rapidly,” Huang and colleagues wrote.

Common adverse events (AEs) included fever and hypoxia. Most AEs that occurred in more than 1 participant were grade 1 or 2 except for 1 case of grade 3 hypoxia. There were no cases of severe cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Elevated interleukin-6 (IL-6) levels in the cerebrospinal fluid were the most common abnormal lab finding but IL-6 blood concentrations were low after administration.

Patients responded to MT026, with 1 complete response, 4 partial responses, and 1 case of stable disease for an overall response rate of 83.3% and a disease control rate of 100%. Survival data were favorable compared to the normal disease course, with patients having a mean overall survival of 9.8 (max, 17.5) and a mean progression-free survival rate of 5.0 (max, 7.9). Patients had a 66.7% 12-month survival rate after recurrence compared to 15% in history data. Similarly, mean survival duration after recurrence was 15.2 months (max, 33.4) compared to less than 9 months in history data.

“Intra-lumbar injection of IL13Ra2 UCAR-T cells is safe and well tolerated in humans, and IL13Ra2 UCAR-T cells have potent anti-tumor activity for recurrent high-grade glioma. Off-the-shelf allogeneic universal CAR-T therapy is a potential option for treatment of solid malignancies with rapid progression and difficulty collecting tissues,” Huang and colleagues concluded.

Click here to read more coverage of ESMO Congress 2022.

REFERENCE
Huang Y, Shang X, Li X. The clinical results of an investigator initiated trial of allogeneic CAR-T cells targeting IL13Rα2 in the treatment of high-grade glioma. Presented at: ESMO Congress 2022, September 9-13, Paris, France. Poster #300P.