IL4R-Targeting Toxin MDNA55 Yields Promising OS in Recurrent Glioblastoma


MDNA55 appears tolerable and effective in a cohort of patients enrolled in a phase 2b trial, showing sustained efficacy in subgroup analyses.

IL4R-Targeting Toxin MDNA55 Yields Promising OS in Recurrent Glioblastoma | Image Credit: © crevis -

“The median OS benefit of MDNA55 treatment is encouraging, particularly in a population that is known to have a poor prognosis," according to the authors of a phase 2b study (NCT02858895).

The interleukin 4 receptor (IL4R)­–targeting toxin MDNA55 tolerably achieved tumor control and extended survival across a cohort of patients with de novo, IDH wild-type, nonresectable, recurent glioblastoma, according to findings from a phase 2b trial (NCT02858895) published in Neuro-Oncology.

In the intent-to-treat (ITT) population (n = 47), median overall survival (OS) was 10.2 months (one-sided 80% CI, 8.39-12.75), and the corresponding figure in the per protocol (PP) population (n = 44) was 11.64 months (one-sided 80% CI, 8.62-15.02), thereby meeting the primary end point. The OS rates at 12 months were 43% (95% CI, 29%-57%) and 46% (95% CI, 31%-60%) in the ITT and PP populations, respectively.

Furthermore, subgroup analyses indicated a median OS of 15.02 months (95% CI, 7.70-16.43) among patients with high IL4R expression and a median of 8.39 months (95% CI, 5.67-12.75) among those with low expression. However, this difference was not statistically significant (P = .215). OS rates at 12 months were 57% and 33% in each respective subgroup.

Tumor shrinkage or stabilization occurred in 31 of 41 patients, with evidence of a durable complete response (CR) in 1 patient. The tumor control rate (TCR) was 75.6% in the total population and 81% among patients with IL4R-high or IL4R-low disease treated with a high dose of MDNA55. The median progression-free survival (PFS) according to radiologic-only assessment was 3.61 months (95% CI, 2.62-7.70). The PFS rate was 33% at 6 months, 27% at 9 months, and 27% at 12 months.

“Currently, treatment options following the recurrence of primary glioblastoma are very limited and not effective,” the investigators wrote. “The median OS benefit of MDNA55 treatment is encouraging, particularly in a population that is known to have a poor prognosis.”

These findings come from a single-arm, non-randomized, open-label phase 2b study, in which patients enrolled between March 2017 and September 2019 in the United States and Poland. The median age of this population was 56 years (range, 34-78), and was mostly comprised of male patients (63.8%).

The mean maximal tumor diameter at baseline was 30.8 mm, and the median time between initial diagnosis and the start of treatment was 12.72 months (range, 5.15-44.23). All patients underwent surgery at their initial diagnosis and had tumors unsuitable for resection at relapse. Prior temozolomide (Temodar) treatment and prior radiotherapy had been administered to all but 1 patient. Most patients (78.7%) had experienced 1 relapse, and the remainder (21.3%) had experienced 2.

In sum, 18 patients (38.3%) had methylated MGMT, 24 (51.1%) had unmethylated MGMT, and 5 (10.6%) had no relevant data available. IL4 expression was high in 23 patients (49%) and low in 19 (40%).

Investigators placed 1 to 4 infusion catheters for treatment administration using stereotactic surgery and then administered intra- and peritumoral infusion of MDNA55 using convection-enhanced delivery. Treatment consisted of a single infusion at a concentration of 1.5 µg/mL to 9.0 µg/mL and a volume no greater than 66mL. The pre-determined total dose was 18µg to 240µg. Infusion durations did not surpass 48 hours, and the flow rate of each catheter did not surpass 10 μL/min.

The median total dose was 180 µg (range, 18.0-240.3), the median infusion volume was 30 mL (range, 12-66), and the median infusion duration was 26.57 hours (range, 15.46-57.21).

The primary end point, OS in the ITT population, was compared against a null hypothesis of 8.0 months, derived from a clinically-weighted average of published studies assessing FDA-approved therapies. PFS and objective response rate were secondary end points.

The most frequent adverse effects (AEs) were seizure (42.6%), fatigue (40.4%), headache (38.3%), and muscular weakness (31.9%). AEs deemed possibly related to the drug or infusion procedure affected 32 patients (68.1%), and the most common of these were seizure (21.3%), fatigue (19.1%), headache (17.0%), and pyramidal tract syndrome (17.0%).

Grade 5 AEs occurred in 8 patients, 6 of which were deemed unrelated to the study treatment.

“Combining targeted treatment and advanced drug delivery techniques employed in this study provides opportunities to potentially deliver substantive benefit in patients with recurrent glioblastoma and to explore the efficacy of MDNA55 in a pivotal trial,” the investigators concluded.


Sampson JH, Singh Achrol A, Aghi MK, et al. Targeting the IL4 receptor with MDNA55 in patients with recurrent glioblastoma: results of a phase IIb trial. Neuro Oncol. 2023;25(6):1085-1097. doi:10.1093/neuonc/noac285

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