Journal Publication

Ivonescimab plus chemo shows early activity in two recurrent H3K27M glioma cases

A two-patient pilot report finds partial tumor shrinkage and tolerability with an anti-PD-1/VEGF bispecific in a cancer with a typical median survival under a year.

By AppliedXLJuly 14, 2026

Executive Summary

A pilot case report describes two patients with a uniformly fatal pediatric-type brain tumor who responded to a bispecific antibody combined with chemotherapy after their disease progressed on standard treatment.
The tumor type has no established salvage option once chemoradiotherapy fails, and both patients in this report lived well beyond the disease's typical survival window while tolerating the regimen without severe toxicity.
The drug simultaneously blocks two targets, an immune checkpoint and a vascular growth factor, testing whether combining immune reactivation with vascular normalization can overcome a tumor microenvironment that has resisted single-mechanism approaches.
The findings come from two patients treated off-label outside a controlled study, so the results demonstrate feasibility and tolerability rather than an established survival benefit.

The stakes

H3K27M-mutant diffuse midline glioma is an aggressive, immunosuppressive brain tumor that resists conventional chemoradiotherapy. Median overall survival after diagnosis typically runs 8 to 11 months, fewer than 10% of patients survive beyond two years, and five-year survival generally sits below 1%. No therapy has established a durable salvage option for patients who progress after first-line treatment and are not candidates for repeat radiotherapy. Pilot

How it was done

Two patients with recurrent H3K27M-mutant disease who progressed rapidly after standard first-line chemoradiotherapy received off-label ivonescimab at 10 mg/kg intravenously every three weeks, combined with chemotherapy, for five to six cycles. Ivonescimab is a bispecific antibody designed to block PD-1, an immune checkpoint, and VEGF, a vascular growth factor, simultaneously, with the rationale that restoring T-cell activity and normalizing tumor blood vessels together might overcome resistance that single-mechanism drugs have not. Pilot

The result

MRI scans showed tumor shrinkage after three cycles, alongside improvement in Karnofsky Performance Status, a measure of functional ability. At treatment completion, both patients had achieved partial remission, with tumor volume reductions of 66.7% and 68.7%. Both maintained progression-free survival beyond 8 months and overall survival beyond 16 months, and both remained alive more than 10 months after recurrence. Pilot

Tolerability

The combination was tolerated without grade 3 or higher adverse events in either patient. The most common toxicities were fatigue, blood-count abnormalities, and nausea or vomiting. In a population where treatment options are limited by both tumor aggressiveness and eligibility for repeat radiation, tolerability alongside signs of tumor response is itself a relevant finding for a population with few alternatives. Pilot

What it doesn't establish

The report covers two patients without a comparator arm, so it demonstrates that the regimen is feasible and was tolerated rather than proving a survival benefit over other salvage approaches. The authors themselves note that larger, more rigorous studies are needed to define the efficacy and safety of this strategy in diffuse midline glioma. Pilot

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