MDNA55 Increases Survival in Glioblastoma, Notably in Patients With High ILR4 Levels, Early Trial Data Show

MDNA55 Increases Survival in Glioblastoma, Notably in Patients With High ILR4 Levels, Early Trial Data Show

The investigational therapy MDNA55 increases survival in people with recurrent glioblastoma, a type of brain cancer — especially in those who produce high levels of ILR4, a marker of aggressive disease, updated results of a clinical trial show.

Fahar Merchant, president and CEO of Medicenna Therapeutics, MDNA55’s developer, presented the findings at the inaugural Targeting Innate Immunity Congress, held recently in Cambridge, Mass.

MDNA55 is a fusion protein that combines interleukin-4 (IL-4) and a modified toxin from the bacteria Pseudomonas. The receptor that binds IL-4 (IL-4R) is overly produced by tumor cells, especially those in glioblastoma, and by cells in the tumor microenvironment that repress the immune response against the tumor.

The tumor microenvironment is composed of non-tumors cells that hide the tumor from the immune system. Thus, the tumor microenvironment significantly contributes to cancer progression.

“We’re beginning to truly understand and appreciate … the many layers of immunosuppression that evolve to protect and prevent an immune attack on the tumor,” Merchant said in a press release.

“This means it is necessary to find a sustained way to break down the tumor’s protective walls, as well as attack the tumor itself. The multi-pronged approach utilized by MDNA55 allows us to do just that,” he added.

The pseudomonas toxin is only active in cells where IL-4 interacts with its receptor, so MDNA55 is a potential treatment for glioblastoma and other types of cancer. It attacks the tumor and immunosuppressive cells, while leaving other cells unharmed.

This Phase 2b trial (NCT02858895) is assessing the safety and efficacy of a single treatment with MDNA55 in people with glioblastoma that has returned or progressed after one or two prior treatments.

The study enrolled 46 participants who received one of two doses — low or high — of MDNA55 applied by Convection Enhanced Delivery (CED). This technique involves inserting catheters in the brain to ensure a precise delivery near the tumor site.

At the presentation, Merchant reported that participants treated with the low dose lived for a median of 11.8 months, while those in the high-dose group survived a median of 16.7 months. This exceeds the median survival of 8-9 months observed with approved treatments for glioblastoma.

People with high amounts of IL-4R experienced the highest benefits from the therapy, the results showed. Among those in the low-dose group, survival was a median of 13.6 months for patients with high IL-4R, and 8.1 months for those with low IL-4R. Similarly, in the high-dose group, survival was 15.2 months for those with high IL-4R, and 8.5 months for those with low IL-4R.

Participants whose tumor shrank or stopped growing after treatment lived longer (16.1 months) than those with progressive disease (8.3 months).

Complete safety data of patients treated with the high dose are in agreement with previous results, showing that MDNA55 does not cause toxicity outside the tumor. There were no treatment-related deaths.

“The data continues to show very promising results for MDNA55 when compared to approved therapies for rGBM [recurrent glioblastoma]. These new findings are consistent with previous results showing that patients suffering from rGBM, particularly those with the IL4R biomarker an indicator of a more aggressive form of rGBM, are surviving substantially longer with just one treatment,” Merchant said.

“This is very exciting for both Medicenna and the broader health community, as this not only offers considerable benefit to patients with [rGMB] but also offers hope for patients with at least 20 other cancer indications where the tumor and associated tumor microenvironment over-expresses the IL4R.”

The complete results of the trial are expected by the end of 2019.

Alejandra has a PhD in Genetics from São Paulo State University (UNESP) and is currently working as a scientific writer, editor, and translator. As a writer for BioNews, she is fulfilling her passion for making scientific data easily available and understandable to the general public. Aside from her work with BioNews, she also works as a language editor for non-English speaking authors and is an author of science books for kids.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Alejandra has a PhD in Genetics from São Paulo State University (UNESP) and is currently working as a scientific writer, editor, and translator. As a writer for BioNews, she is fulfilling her passion for making scientific data easily available and understandable to the general public. Aside from her work with BioNews, she also works as a language editor for non-English speaking authors and is an author of science books for kids.
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