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
Mustang Bio, Inc. announced Phase 1 clinical data published in Nature Medicine showing promising safety and clinical activity of MB-101 CAR T-cell therapy for recurrent malignant glioma, including glioblastoma. Patients achieved stable disease or better in 50%, with two partial responses and two complete responses. The therapy exhibited a 70% improvement in median overall survival compared to expected rates, with well-tolerated delivery methods and manageable adverse events.
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MB-101 CAR T-cell therapy by Mustang Bio, Inc. demonstrated promising safety and clinical activity in Phase 1 clinical data published in Nature Medicine.
50% of patients achieved stable disease or better, with two partial responses and two complete responses, including a 70% improvement in median overall survival compared to expected rates.
The therapy was well-tolerated with various delivery methods and manageable adverse events, paving the way for future studies and potential transformative treatment approaches.
The clinical data from the Phase 1 trial of MB-101 presents a significant advancement in the treatment of recurrent and refractory malignant glioma. The promising outcomes, particularly the complete responses and the improvement in median overall survival, suggest that the direct administration of IL13Rα2-targeted CAR T-cells could be a viable therapeutic option for patients with glioblastoma (GBM), a notoriously difficult-to-treat brain cancer. The correlation between pre-treatment 'hot' tumor microenvironments and survival benefit is particularly noteworthy, as it may guide patient selection and therapeutic strategies in future clinical applications.
The data indicating a ~70% improvement in median overall survival is a critical metric for evaluating the potential market impact of MB-101. The safety profile, characterized by the absence of dose limiting toxicities and manageable adverse events, is equally important from a regulatory and commercialization standpoint. The ability to achieve stable disease or better in half of the heavily pretreated patient population is a notable outcome that could position MB-101 favorably in the competitive landscape of GBM treatments. Furthermore, the dual intratumoral and intraventricular delivery approach represents an innovative strategy that may set a new standard for CAR T-cell therapies in solid tumors.
The largest reported trial to date of CAR-T therapy for solid tumors signifies a potential shift in the oncology market, especially for therapies targeting GBM. The clinical success of MB-101 could influence investor sentiment and stock valuations not only for Mustang Bio but also for other companies developing similar therapies. The trial outcomes could stimulate increased investment in CAR-T and other cell therapies for solid tumors. It is essential to monitor the long-term clinical benefits and the scalability of the manufacturing process, as these factors will play a crucial role in the therapy's market adoption and pricing strategies.
03/07/2024 - 07:30 AM
MB-101 was well-tolerated and 50% of patients achieved stable disease or better with two partial responses and two complete responses lasting 7.5 and 66+ months, respectively
~70% improvement in median overall survival compared to expected survival rate in cohort with dual intratumoral (ICT)/ intraventricular (ICV) delivery and an optimized manufacturing process
This is the largest reported trial to date of CAR-T therapy for solid tumors
WORCESTER, Mass., March 07, 2024 (GLOBE NEWSWIRE) -- Mustang Bio, Inc. (“Mustang”) (Nasdaq: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for difficult-to-treat cancers and rare genetic diseases, today 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 IFNγ, CXCL9, and CXCL10, were associated with CAR T-cell administration and bioactivity. Dr. Christine Brown, Heritage Provider Network Professor in Immunotherapy, deputy director of the T-Cell Therapeutics Research Laboratories at City of Hope, and lead author on the publication, said, “These Phase 1 clinical trial results represent a significant step forward in our understanding of the potential of MB-101 CAR T-cell therapy to treat recurrent GBM, an extremely aggressive tumor with very limited treatment options. One of the main challenges for treating brain cancer is that medications have difficulty crossing the blood-brain barrier. To overcome that barrier, the trial delivered CAR T-cells directly into the brain tumor and the cerebrospinal fluid, the fluid that protects and surrounds the brain and spinal cord. Repetitive locoregional administration of IL13Rα2-CAR T-cells was feasible and well-tolerated with no dose limiting toxicities, even at the highest dose level of 200 x 106 CAR T-cells per infusion. The safety and promising therapy-related bioactivity data pave the way for future studies of MB-101 and offer hope for a transformative treatment approach. We look forward to continuing our work with Mustang on this promising therapy.”
Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, “MB-101 has demonstrated compelling therapeutic potential, including delivering unprecedented complete responses in two high-grade glioma patients; the first patient who achieved a complete response was published in The New England Journal of Medicine . These two patients treated solely with MB-101 both had high levels of intratumoral CD3+ T-cells pre-therapy (i.e., “hot” tumors) and achieved complete responses lasting 7.5 and 66+ months, respectively. This trial has led to several other studies using MB-101, including supporting our upcoming novel combination clinical trial of MB-109 [MB-101 (IL-13Rα2 targeted CAR T-cell therapy) + MB-108 (HSV-1 oncolytic virus)] to improve treatment of recurrent GBM and high-grade astrocytoma. The combination leverages initial treatment with MB-108 to reshape the tumor microenvironment and make immunologically “cold” tumors “hot,” thereby potentially enabling the MB-101 CAR T-cell therapy to achieve efficacy equivalent to that seen in intrinsically “hot” tumors in this City of Hope Phase 1 trial.”
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 IL13Rα2-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 IL13Rα2-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.
A link to the Nature Medicine publication can be found here .
Dr. Brown has a financial interest in Mustang and has previously been a paid consultant for the company.
Additional information on the Phase 1 study can be found on www.ClinicalTrials.gov NCT02208362
About Mustang Bio www.mustangbio.com
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Company Contacts: ir@mustangbio.com
What Phase was the clinical data on MB-101 published in?
The Phase 1 clinical data on MB-101 was published in Nature Medicine.
What percentage of patients achieved stable disease or better with MB-101 therapy?
50% of patients achieved stable disease or better with MB-101 therapy.
What were the two complete responses achieved with MB-101 therapy?
Two complete responses were achieved, lasting 7.5 and 66+ months, respectively.
What improvement in median overall survival was reported with MB-101 therapy?
MB-101 therapy showed a 70% improvement in median overall survival compared to expected rates.
What organization developed MB-101 CAR T-cells?
City of Hope developed MB-101 CAR T-cells and exclusively licensed them to Mustang Bio, Inc.
