The FDA has accepted Mustang Bio’s investigational new drug (IND) application for a phase 1 clinical trial evaluating the combination of MB-101chimeric antigen receptor (CAR) T-cell therapy and MB-108 oncolytic virus in patients with recurrent glioblastoma and high-grade astrocytoma, termed MB-109.1
“We are very pleased with the FDA’s acceptance of our IND application for MB-109, which allows Mustang to initiate a Phase 1 clinical trial to further evaluate combining MB-108 and MB-101, an attractive strategy for improving outcomes for patients with recurrent GBM and high-grade astrocytomas. Recurrent GBM remains a major challenge to treat, with a median overall survival rate of 6 months. We are committed to finding better treatment options for patients living with difficult-to-treat cancers and look forward to initiating our MB-109 Phase 1 clinical trial in 2024,” Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said in a statement.1
MB‐101 is a City of Hope-developed IL13Rα2‐targeted CAR-T cell therapy and MB-108 is a Nationwide Childrens-developed Herpes simplex virus-1 oncolytic virus. MB-108 is designed to make the cold tumor “hot” by reshaping the tumor microenvironment through recruitment of endogenous CD8- and CD3-positive effector T-cells and may improve the infiltration and efficacy of the MB-101 CAR T-cell therapy. Investigators first inject MB-108 before infusing MB-101.
WATCH NOW: Mazyar Shadman, MD, MPH, on MB-106's Potential in Follicular Lymphoma
“The fact that this will be the first ever industry-sponsored trial to combine a CAR-T cell therapy with an oncolytic virus underscores Mustang’s commitment to innovation in the oncology and cell therapy space. Furthermore, FDA acceptance of our IND within 30 days of initial submission – despite the innovative aspect of the combination therapy and the complexity of the trial design – is testimony to the talent and resourcefulness of our team,” Litchman added.1
Clinical Takeaways
- The FDA has accepted Mustang Bio's IND application for a phase 1 clinical trial to evaluate the combination of MB-101 CAR T-cell therapy and MB-108 oncolytic virus in patients with recurrent glioblastoma and high-grade astrocytoma (MB-109).
- MB-101 is an IL13Rα2-targeted CAR-T cell therapy while MB-108 is a HSV-1 oncolytic virus designed to enhance the tumor microenvironment and improve the efficacy of MB-101.
- Mustang Bio has recently reported promising data on MB-106, a CD20-targeted CAR T-cell therapy, in patients with indolent lymphoma, with encouraging responses observed.
Mustang most recently announced data on MB-106, Mustang Bio’s CD20-targeted CAR T-cell therapy, from a phase 1/2 clinical trial (NCT05360238) in patients with indolent lymphoma. Investigators found that all 4 patients with relapsed/refractory indolent non-Hodgkin lymphoma (NHL) responded to the starting dose of 3.3 x 106 CAR T-cells/kg, with 2 complete responses (CRs) in patients with follicular lymphoma. One patient with Waldenstrom macroglobulinemia (WM) had a complete metabolic response, and another patient with hairy cell leukemia has continued to have stable disease at over 6 months post-treatment.
“MB-106 continues to show potential as an immunotherapy option for patients with a wide range of hematologic malignancies, including patients previously treated with CD19-directed CAR-T cell therapy,” Mazyar Shadman, MD, MPH, study chair and Innovators Network Endowed Chair, Fred Hutch, and Associate Professor and physician, University of Washington, said in an August statement.2 “We are excited that the first data from the expanded evaluation of MB-106 are similar in safety as what we’ve seen to date in the ongoing Phase 1/2 clinical trial at Fred Hutch. Additionally, the data from the ongoing clinical trial at Fred Hutch continue to demonstrate a high rate of complete and durable responses.”
REFERENCES
1. Mustang Bio announces FDA acceptance of IND application for MB-109, a novel combination of MB-101 (IL13Rα2‐targeted CAR-T cell therapy) and MB-108 (HSV-1 oncolytic virus), for the treatment of recurrent glioblastoma and high-grade astrocytoma. News release. Mustang Bio. October 26, 2023. https://ir.mustangbio.com/news-events/press-releases/detail/168/mustang-bio-announces-fda-acceptance-of-ind-application-for
2. Mustang Bio announces first data from ongoing multicenter phase 1/2 clinical trial evaluating MB-106 CAR-T cell therapy. News release. Mustang Bio. https://ir.mustangbio.com/news-events/press-releases/detail/166/mustang-bio-announces-first-data-from-ongoing-multicenter
