MB-101 Receives FDA Orphan Drug Designation for Astrocytoma and Glioblastoma

The FDA has granted orphan drug designation to the IL13Rα2-targeted CAR T-cell therapy MB-101 for the treatment of patients with recurrent diffuse and anaplastic astrocytoma and glioblastoma.1

“We are thrilled that MB-101 received orphan drug designation on time and with a designation that is broader than the indication proposed,” Manuel Litchman, MD, president and chief executive officer of Mustang Bio, stated in a news release. “The orphan drug designation for MB-101, coupled with the orphan drug designation granted previously for MB-108, is strong validation for our science, as we hope to advance MB-101, in combination with MB-108, as a potential treatment option for patients living with malignant glioma, including patients with recurrent glioblastoma and high-grade astrocytomas. Our novel therapeutic strategy, combining our MB-101 CAR-T cell therapy with our MB-108 oncolytic virus, leverages MB-108 to reshape the tumor microenvironment to make cold tumors ‘hot,’ thereby potentially improving the efficacy of MB-101 CAR-T cell therapy. This progress demonstrates our dedication to exploring new possibilities for improving outcomes in patients with challenging-to-treat cancers.”

MB-101 and MB-108 together are referred to as MB-109; the CAR T-cell therapy was developed at City of Hope in Duarte, California, and MB-108—an HSV-1 oncolytic virus—is being licensed from Nationwide Children’s Hospital in Columbus, Ohio. MB-109 is intended to turn immunologically cold tumors into hot tumors via MB-108 through the recruitment of endogenous CD8- and CD3-positive effector T cells, thus increasing the efficacy of subsequent administration of MB-101.

Previously reported data from a phase 1 trial (NCT02208362) showed that among evaluable patients (n = 58) with recurrent and refractory malignant glioma, including glioblastoma, 50% achieved a best response of stable disease or better for at least 2 months.2 This included 1 complete response (CR), 2 partial responses, and 1 subsequent CR following additional cycles of CAR T-cell therapy.

Notably, in patients with recurrent glioblastoma treated in the final cohort with dual intratumoral and intraventricular delivery with an agent created via an optimized manufacturing process, the median overall survival (OS) was 10.2 months. In all evaluable patients, the median OS was 8 months.

All delivery methods, including intratumoral and intraventricular delivery alone or together, were well tolerated at doses up to 200×106 CAR T cells.

The phase 1 study enrolled patients 12 to 75 years of age with previously diagnosed, histologically confirmed grade III or IV glioma, or grade II glioma with radiographic progression consistent with a grade III or IV disease following standard therapy.3 All patients needed to have radiographic evidence of progression or recurrence of measurable disease more than 12 weeks after the completion of initial radiation therapy. Other key inclusion criteria comprised a Karnofsky performance status of at least 60% and a life expectancy of more than 4 weeks.

In the dose-escalation study, patients received MB-101 an initial low dose in cycle 1, followed by 2 additional higher doses in cycles 2 and 3. Additional treatment cycles with the agent given up to the highest tolerated dose were allowed in cycle 4 and beyond. The trial evaluated different delivery methods for MB-101, including intraventricular; intraventricular/intracavitary; intraventricular; and dual delivery.

Investigators evaluated the following dosing schedules:

1. Schedule 1: 2x106 CAR T cells in cycle 1 plus 10x106 CAR T cells in cycles 2 and 3 for a total dose of 22x106 CAR T cells. Optional subsequent cycles used doses of no more than 10x106 CAR T cells.
2. Schedule 2: 10x106 CAR T cells in cycle 1 plus 50x106 CAR T cells in cycles 2 and 3 for a total dose of 110x106 CAR T cells. Optional subsequent cycles used doses of no more than 50x106 CAR T cells.
3. Schedule 3: 20x106 CAR T cells in cycle 1 plus 100x106 CAR T cells in cycles 2 and 3 for a total dose of 220x106 CAR T cells. Optional doses were given at no more than 100x106 CAR T cells.

The incidence of grade 3 or higher CAR T-cell therapy–related adverse effects, along with the rate of dose-limiting toxicities, served as the trial’s primary end points. Secondary end points comprised responses per RANO criteria and 6-month OS rate.

References

1. Mustang Bio granted orphan drug designation by U.S. FDA for MB-101 (IL13Ra2-targeted CAR T-cells) to treat astrocytomas and glioblastoma. News release. July 7, 2025. Accessed July 8, 2025. https://ir.mustangbio.com/news-events/press-releases/detail/192/mustang-bio-granted-orphan-drug-designation-by-u-s-fda-for
2. Mustang Bio announces publication in Nature Medicine of data from phase 1 trial evaluating MB-101 IL13Rα2-targeted CAR T-cells in high-grade glioma. News release. March 7, 2024. Accessed July 8, 2025. https://ir.mustangbio.com/news-events/press-releases/detail/175/mustang-bio-announces-publication-in-nature-medicine-of
3. Genetically modified T-cells in treating patients with recurrent or refractory malignant glioma. ClinicalTrials.gov. Updated February 19, 2025. Accessed July 8, 2025. https://clinicaltrials.gov/study/NCT02208362