ASCO 2025 | Phase I trial of ICV-delivered bivalent CAR T-cells in glioblastoma
Stephen Bagley, MD, MSCE, University of Pennsylvania, Philadelphia, PA, discusses results from the Phase I trial (NCT05168423) of bivalent CAR T-cells targeting EGFR and IL13Rα2 intracerebroventricularly (ICV) delivered in recurrent glioblastoma (rGBM). Treatment was generally feasible, with expected neurotoxicities and evidence of robust CAR T-cell expansion in cerebrospinal fluid. Many patients experienced measurable tumor shrinkage, with one durable stable disease case exceeding one year. This interview took place during the 2025 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
Sure. So we presented the full results of the dose escalation and dose expansion phases of our phase one trial. And this is a bicistronic CAR that dual targets EGFR and IL-13 receptor alpha-2. And the product is delivered intracerebroventricularly. So that is a direct injection into the spinal fluid using an Ommaya reservoir that gets placed into the patient’s lateral ventricle of the brain...
Sure. So we presented the full results of the dose escalation and dose expansion phases of our phase one trial. And this is a bicistronic CAR that dual targets EGFR and IL-13 receptor alpha-2. And the product is delivered intracerebroventricularly. So that is a direct injection into the spinal fluid using an Ommaya reservoir that gets placed into the patient’s lateral ventricle of the brain. And so we reported on the 18 patients. And this is a phase one first-in-human trial. So of course, establishing the toxicity profile and the safety profile and identifying the maximum tolerated dose and the recommended dose for expansion were really important endpoints, which we were able to do. We now have a much better sense of the toxicity profile, which is essentially fevers and acute neurotoxicity, both of which are reversible and manageable. And we identified 25 million cells as both the maximum tolerated dose and the recommended dose for expansion that we’re using moving forward. We were able to see a really excellent expansion of the T cells, both in the spinal fluid and also to some extent in the blood of all of these patients. And we saw some exciting early efficacy signals. It’s a phase one, you know, small study. So none of this can be really, you know, reliable until we do larger studies. But we do see a fairly high rate of tumor shrinkage, which we generally don’t see with other things in glioblastoma. And we do have a small subset of patients who have had durable disease control. And this has included a patient who entered the trial with leptomeningeal disease, which typically carries a week to a couple of months life expectancy in glioblastoma. That individual was over 16 months without any tumor recurrence at the time that we had data cut off for the presentation. So that was a case of a very remarkable responder. But unfortunately, a lot of the other patients do progress within a few months of the first treatment. So moving forward, we’re, of course, working hard to identify mechanisms of resistance and try to design the next versions of this product and combinatorial approaches and other things to increase that response rate and increase the durability of the response.
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