Mustang Bio, Inc. announced Phase 1 clinical data were published in Nature Medicine that demonstrated the promising safety and clinical activity of Mustang's MB-101 (IL13Ra2-targeted CAR T-cells) for the treatment of patients with recurrent and refractory malignant glioma, including glioblastoma. MB-101 was developed by City of Hope, one of the largest cancer research and treatment organizations in the United States, and exclusively licensed to Mustang. Highlights from the data include: Stable disease or better was achieved in 50% (29/58) of heavily pretreated patients for at least two months, with two partial responses, one complete response (CR), and a second CR after additional CAR-T cycles under compassionate use; Patients with recurrent GBM treated in the final cohort with dual intratumoral (ICT)/intraventricular (ICV) delivery and an optimized manufacturing process exhibited superior median overall survival of 10.2 months, compared to the expected survival rate of six months in patients with recurrent GBM.

The median overall survival for all patients was eight months; Intermediate/high pre-treatment tumor T-cell levels that are indicative of a ?hot? tumor microenvironment (TME) correlated with a significant survival benefit over negative/low pre-treatment tumor T-cell levels that are indicative of a ?cold? TME; Overall, all routes of delivery (ICT, ICV and dual ICT?+?ICV) were well-tolerated at doses up to 200×106 CAR?T-cells; Central nervous system (CNS) increases in inflammatory cytokines, including IFN?, CXCL9, and CXCL10, were associated with CAR T-cell administration and bioactivity.

The data reported on 65 patients with recurrent high-grade glioma, the majority being glioblastoma (GBM; 2?+?recurrences); 58 patients were evaluable for disease response. Primary endpoints were safety and feasibility, with secondary endpoints measuring therapy-related cytokine dynamics, CAR T-cell persistence and clinical outcomes. Patients were treated at one of three dose schedules with three weekly infusions administered without prior lymphodepleting chemotherapy and were evaluated one week after the third cycle for dose limiting toxicities.

Additional infusions were allowed, and patients were followed for toxicities, response, and survival until they progressed or required subsequent therapy. This study evaluated five treatment arms: Arm 1, intratumoral following biopsy (ICT Biopsy); Arm 2, intratumoral following maximal surgical resection (ICT Resection); Arm 3, intraventricular (ICV); and Arms 4 and 5, combined ICT and ICV delivery (Dual ICT?+?ICV). ICV delivery (Arm 3) was added after trial initiation based on clinical experience, in which IL13Ra2-CAR T-cells that were administered ICV mediated a complete response in a patient with multifocal recurrent GBM, and preclinical data suggested ICV was more effective against multifocal tumors.

Subsequently, City of Hope transitioned to dual delivery combining both ICV and ICT (Arms 4?5) ? rather than continuing with ICV alone ? as preclinical data also suggested that intratumoral delivery was more effective for defined unifocal tumors in comparison to ICV-only delivery.

Weekly ICT and/or ICV administration of IL13Ra2-CAR T-cells was well-tolerated, with clinically manageable adverse events. No high-grade cytokine release syndrome or immune effector cell-mediated neurotoxicity adverse events were observed, and no dose limiting toxicities (DLTs) were noted during the 28-day dose limiting toxicity period. The most common toxicities with possible or higher attribution to CAR T-cells were fatigue, headache, and hypertension.

Grade 3 and above toxicities with possible or higher attribution to CAR T-cells were seen in 35% of patients, including two incidences of transient grade 4 cerebral edema with possible attribution to CAR T-cells and one grade 3 encephalopathy and one grade 3 ataxia with probable attribution to CAR T-cells.