NEW YORK – BrainChild Bio on Tuesday said it will begin testing the activity of its autologous CAR T-cell therapy BCB-276 in children and young adults with diffuse intrinsic pontine glioma (DIPG) within a registrational trial by year-end.
The announcement follows the publication of a study today in Nature Medicine, which showed that children and young adults with DIPG who received repetitive doses of B7-H3-targeted CAR T cells tolerated and appeared to benefit from the treatment. According to BrainChild, the preliminary signs of efficacy in this Phase I study warrant further investigation in a Phase II trial. After meeting with the US Food and Drug Administration, the Seattle-based firm has decided to proceed directly to a multicenter Phase II pivotal trial with the aim of generating data on BCB-276 that it can submit to the FDA within a biologics license application.
In the investigator-led Phase I BrainChild-03 trial, scientists from Seattle Children's Research Institute and elsewhere are evaluating BCB-276 in DIPG and recurrent or refractory pediatric central nervous system tumors. In Arm C of the trial, which focused on DIPG, 21 patients received BCB-276 every other week for three weeks, followed by a week off, and then every other week for another three weeks. Following evaluation of their progress by MRI, patients may opt to continue receiving additional courses of BCB-276, if additional T cells are available.
The researchers were primarily interested in determining whether sufficient CAR T cells could be manufactured to complete two courses of treatment and whether the therapy could be administered via an indwelling brain catheter to enable the T cells to directly interact with tumor cells. At the same time, though, they also tracked patients' responses to the treatment. Out of 18 patients evaluable with neuroimaging, one had a partial response, 15 had stable disease, and two had progressive disease.
The median survival among all 21 patients treated in the trial from their initial CAR T-cell infusion was 10.7 months and the median survival from diagnosis was 19.8 months. Among the 12 patients who began CAR T-cell treatment after disease progression, the median survival from the initial CAR T-cell infusion was 9.4 months and median survival from diagnosis was 20.1 months. Among the nine patients who began treatment before progression, median survival following their initial infusion was 13.6 months and median survival from diagnosis was 19.5 months. Of the three patients who are still alive after more than four years of follow-up, one has discontinued therapy and two are still on therapy.
In a statement, BrainChild Bio said the data, though preliminary, suggest a "meaningful improvement" in overall survival for DIPG patients in the pre-progression and post-progression settings compared to current standard of care. Standard palliative focal radiation therapy, by comparison, has a median survival from diagnosis of eight months to 11 months.
Seattle Children's has handed off development of BCB-276 to BrainChild, which spun out of the institute in December 2023 to advance its CAR T-cell therapies.
"We look forward to continuing to work with the FDA and to generate the additional data required to support a successful [investigational new drug] submission leading to the initiation of the BCB-276 pivotal trial by the end of 2025," BrainChild Founder and CSO Michael Jensen said in a statement.