FDA Accepts IND Application of MB-109 for GBM and High-Grade Astrocytoma

• MB-109 is a novel combination of MB-101, an IL13Rα2‐targeted chimeric antigen receptor (CAR) T-cell therapy, and MB-108, an HSV-1 oncolytic virus.

• MB‐101 and MB-108 have each separately shown promising data and were well-tolerated in preclinical studies of patients with recurrent glioblastoma (GBM).

• A phase 1 study plans to evaluate the safety, tolerability, and efficacy of MB-109 in patients with recurrent GBM and high-grade astrocytoma.

The FDA has accepted the investigational new drug (IND) application of MB-109 for the treatment of recurrent GBM and high-grade astrocytoma, according to Mustang Bio, Inc.¹

With this IND acceptance, a phase 1 multicenter clinical trial at City of Hope (COH) and the University of Alabama at Birmingham (UAB) plans to begin to assess the safety, tolerability, and efficacy of this novel combination, which consists of MB-101 and MB-108, in adult patients with recurrent GBM and high-grade astrocytomas that express IL13Rα2 on the surface of the tumor cells.

The first part of the combination, MB-108, is used to reshape the tumor microenvironment and make cold tumors hot, and works to potentially improve the efficacy of MB-101 CAR T-cell therapy.

“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,” said Manuel Litchman, MD, president and chief executive officer of Mustang Bio, Inc, in a press release.¹ “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.”

Preclinical data of MB-109 were presented at the American Association for Cancer Research (AACR) Annual Meeting in 2022 and support this combination therapy as a potential treatment for patients with recurrent GBM.^2,3

Human Brain Activity: © See Less - stock.adobe.com

According to data presented separately on MB-101 and MB-108, the administration of these therapies was shown to be well-tolerated in patients with recurrent GBM. Complete responses (CRs) were observed in 2 patients who were treated with MB-101 alone and who had high levels of intratumoral CD3+ T cells pre-therapy. These CRs lasted 7.5 months in the first patient and 31+ months in the second, respectively.¹

Among the 53 patients from COH whose data were disclosed at AACR in 2022, the 2 CRs observed were in the 2 patients with the “hottest” tumors prior to treatment with MB-101.

Now, phase 1 trials evaluating MB-101 at COH and of MB-108 at UAB continue to enroll patients, and a planned phase 1 study of MB-109 will evaluate the safety, tolerability, and efficacy of MB-109 in patients with recurrent GBM and high-grade astrocytoma. The study is expected to begin enrolling patients in 2024.

“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,” added Litchman in a press release.¹

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, Inc. October 26, 2023. Accessed October 26, 2023. https://tinyurl.com/yujk9fpd

2. Mustang Bio announces City of Hope, University of Alabama at Birmingham and Nationwide Children’s Hospital abstract accepted for late-breaker poster presentation at the american association for cancer research (AACR) annual meeting 2022. News release. Mustang Bio, Inc. March 9, 2022. Accessed October 26, 2023. https://tinyurl.com/bddz64je

3. Mustang Bio announces a phase 1 clinical trial combining MB-101 (IL13Rα2‐targeted CAR T cell therapy) and MB-108 (C134 oncolytic virus) for the treatment of glioblastoma. News release. Mustang Bio, Inc. April 13, 2022. Accessed October 26, 2023. https://tinyurl.com/4shmzxd2