August 11, 2022

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SNO2020: MDNA55 immunotherapy regimen for recurrent glioblastoma

SNO2020: MDNA55 immunotherapy regimen for recurrent glioblastoma



 

SNO2020: MDNA55 immunotherapy regimen for recurrent glioblastoma.

MDNA55 immunotherapy program can double the survival time of patients with recurrent glioblastoma.

 

SNO2020: MDNA55 immunotherapy regimen for recurrent glioblastoma
Original link: https://www.practiceupdate.com/news/31649/2/1?elsca1=emc_enews_daily-digest&elsca2=email&elsca3=practiceupdate_onc&elsca4=oncology&elsca5=newsletter&rid=MTk5MjY3ODAxODE4S0&lid=10332481

 

The initial results of MDNA55-05 were released in the cloud venue of the SNO conference this year, and the results are encouraging.

MDNA55-05 is an open-label, single-arm clinical trial, led by Professor John Sampson (Academician of the American Academy of Sciences, Professor of Department of Neurosurgery at Duke University) and carried out by professors and scholars at Duke Medical Center. Part of the results were announced at this year’s SNO conference.

 

 

Background

MDNA55 is an immunotherapy drug that mainly targets interleukin 4 (IL-4), which can effectively improve the survival of patients with recurrent glioblastoma (GBM) and inhibit tumor growth.

High-dose use of MDNA55 is theoretically effective for all patients with relapsed GBM, regardless of the patient’s IL-4 receptor expression.

The intensive dosing regimen of MDNA55 can be used as a single drug to treat newly-treated GBM, IDH-negative GBM, relapsed and unresectable GBM, and 50% chance of first or second recurrence of GBM with high expression of IL-4.

 

Experimentation:

The trial selected patients who were registered with the Duke Neurosurgery Center or had medical records as the trial control group, and corrected the baseline gap between the two groups (experimental group and control group) using propensity score weighting.

The primary outcome indicator of the trial is: overall survival (OS) after statistical correction; secondary outcome indicators include: the effect of IL-4 receptors on the patient’s total OS.

 

Preliminary results of the test:

The overall results of the test showed that when the dosage reached 240ug, MDNA55 still showed good safety and patient tolerance.

The median OS of all the trial groups included in the population (44 people) was 11.6 months, and the 1-year survival rate was 46%.

 

In the subgroup analysis, MDNA55 at a dose of 180ug showed the best clinical effect on 32 patients with high and low IL-4 receptor expression. The median OS of the target patient was 15 months, and the 1-year survival rate was 55%.

Using the modified RNAO standard (the standard is mainly to assess the nervous system-related symptoms) to assess tumor progression and control, it was found that 81% of patients had tumors under control (26/32), including those with pseudo-progressive tumors ( 15/26).

 

The median progression-free survival (PFS) of patients with tumor progression control was 4.7 months, and the median OS was 15 months, which was much higher than that of patients with tumor progression.

Their median PFS was 1.0 months, and the median OS Is 7.7 months. Compared with the control group, the corrected OS was 15.7 months, while the control group was 7.2 months (HR=0.52, 95% CI: 0.30-0.91), and OS was prolonged by more than 1 times.

 

Regarding the above results, Professor Sampson explained that MDNA55 is a toxin that targets the IL-4 receptor and is critical in the growth and invasion of GBM.

IL-4 receptors are highly expressed in the tumor microenvironment of GBM, and highly expressed IL-4 receptors are often associated with a worse prognosis of GBM.

MDNA55 can be understood as a genetic fusion of two molecules, which are the cyclically arranged IL-4 superfactor and the catalytic domain of Pseudomonas exotoxin.

As a carrier, highly specific IL-4 can deliver powerful bacterial toxins to tumor cells.

MDNA55 has the potential to eliminate tumors and destroy tumor support networks, and it can reactivate the immune system to fight cancer.

 

Finally, Professor Sampson concluded that the drug MDNA55, which targets the IL-4 receptor, has been proven to improve patient survival time and tumor control, and has the potential to benefit all patients with relapsed GBM regardless of the expression of IL-4 receptor. Happening.

At present, there is no approved treatment that can prolong the OS of recurrent GBM by 50%.

In this trial, MDNA55 can more than double the OS of recurrent GBM, indicating that MDNA55 is a very promising treatment option.

 

 

 

SNO2020: MDNA55 immunotherapy regimen for recurrent glioblastoma

(source:internet, reference only)


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