BrainChild Bio's Pediatric Brain Tumor CAR-T BCB-276 Reels in Breakthrough Therapy Designation

BrainChild Bio's BCB-276, an investigational CAR-T therapy that targets B7-H3 and is being developed for the treatment of a type of pediatric brain tumor referred to as diffuse intrinsic pontine glioma (DIPG), has received breakthrough therapy designation from the FDA.¹

The FDA’s decision was supported by data indicating overall survival benefit for patients with brain tumors from the phase 1 BrainChild-03 clinical trial (NCT04185038), which is being carried out by Seattle Children’s, BrainChild’s academic partner. The company intends to conduct a pivotal phase 2 clinical trial for BCB-276 in order to support a biologics license application for the CAR-T product for children and young adults with DIPG. This study is expected to launch in the fourth quarter of this year. A Type B meeting held between BrainChild and the FDA in late 2024 brought the agency into alignment with the company regarding the plan for the trial.

“Breakthrough therapy designation gives us the possibility to accelerate the development path for BCB-276 as a CAR T-cell therapy that can potentially transform the treatment of DIPG,” Michael Jensen, MD, the founder and chief scientific officer of BrainChild Bio, said in a statement.¹ “This designation is a major milestone for the children and families afflicted with these devastating brain tumors and represents a new paradigm for treating central nervous system brain tumors in children and adults, including a large number of patients suffering with glioblastomas and brain metastases.”

Data from BrainChild-03 were recently published in Nature Medicine.² The results reported specifically pertained to Arm C of the trial, which included only patients with DIPG. The patients were treated with repeated intracerebroventricular (ICV) doses of B7-H3 CAR T-cells. Patients (n = 21) received repeated doses of the CAR-T therapy with intrapatient dose-escalation regimens and no prior lymphodepletion. Participants were not permitted to receive other tumor-directed therapy while receiving the CAR-T. The highest dose of CAR-T administered was 10x10⁷ cells per dose (dose regimen 4, DR4). DR4 was determined to be the maximally tolerated DR.

Median survival for the 21 patients from their initial dose of CAR-T was 10.7 months, with a median survival from diagnosis of 19.8 months. First author Nicholas A. Vitanza, MD, an associate professor of hematology/oncology at Seattle Children’s, and colleagues noted that 3 of the patients were still alive at 44, 45, and 52 months following diagnosis. With regard to safety, the authors stated that headache, fatigue, and fever constituted common adverse events. At DR2, 1 patient experienced a case of intratumoral hemorrhage that was determined to be a dose-limiting toxicity.

“Ultimately, this completed first-in-human trial shows that repetitive ICV dosing of B7-H3 CAR T-cells in pediatric and young adult patients with DIPG is tolerable, including multiyear repeated dosing, and may have clinical efficacy that warrants further investigation on a multisite phase 2 trial,” Vitanza and colleagues wrote in the paper’s abstract.²

The topic of using CAR T-cells to treat brain tumors was recently discussed on the most recent episode of CGTLive®’s video podcast, ImmunoLogic. In the episode, entitled "Breaking the Brain’s Barrier: CAR T-Cells Take on Glioblastoma", guest Marcela Maus, MD, PhD, the director of the Cellular Immunotherapy Program at the Massachusetts General Hospital Cancer Center, spoke about her research into the use of CAR-T therapy to treat glioblastoma. Maus and the cohosts covered topics including challenges and insights from early clinical trials, innovations and clinical results, antigen expression and the possibility of readministration, as well as the autologous versus allogeneic debate.

REFERENCES
1. FDA grants breakthrough therapy designation for BrainChild Bio’s B7-H3 CAR T-cell therapy for incurable pediatric brain tumors. News release. BrainChild Bio, Inc. April 22, 2025. Accessed April 24, 2025. https://www.brainchildbio.com/uploads/BTD_Press_Release_18April2025_FinalforNewswire.pdf
2. Vitanza, NA, Ronsley, R, Choe, M et al. Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial. Nat Med 31, 861–868 (2025). doi: 10.1038/s41591-024-03451-3