FDA Awards RMAT Designation to BCB-276 CAR T-Cell Therapy for Diffuse Intrinsic Pontine Glioma

Diffuse Intrinsic Pontine Glioma

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The FDA has granted regenerative medicine advanced therapy (RMAT) designation to the B7-H3–directed CAR T-cell therapy BCB-276 for the treatment of patients with diffuse intrinsic pontine glioma (DIPG).1

BrainChild Bio, the developer of BCB-276, plans to submit a BLA seeking the FDA approval of BCB-276 for the treatment of pediatric and young adult patients with DIPG based on data from a phase 2 trial, which the company plans to initiate in the fourth quarter of 2025. This clinical plan aligns with an agreement reached between BrainChild Bio and the FDA at a Type B meeting that took place in late 2024.

“It’s gratifying to see another important benchmark reached in our work to combat pediatric brain cancer,” Jeff Sperring, MD, chief executive officer at Seattle Children’s Research Institute in Washington, stated in a news release. “Our research is the foundation of progress to bring potential therapies to kids as fast as we can—and we’re excited about the possibilities afforded by this designation.”

DIPG is a tumor that arises in the brainstem and grows throughout the brainstem's functional anatomy. BCB-276 is designed to be administered locoregionally via an indwelling reservoir-catheter device directly into the cerebrospinal fluid, allowing infused CAR T cells direct access to the tumor bed. This administration method of a B7-H3–directed CAR T-cell therapy was successfully implemented and engendered a survival benefit with BCB-276 in the phase 1b BrainChild-03 trial (NCT04185038).

In April 2025, the FDA granted breakthrough therapy designation to BCB-276 for the treatment of pediatric patients with DIPG based on data from BrainChild-03.2 Results supporting this designation were published in Nature Medicine and showed that among evaluable patients with DIPG (n = 21), the median overall survival was 10.7 months after BCB-276 infusion and 19.8 months after diagnosis.3 Furthermore, 3 patients remained alive at 44 months, 45 months, and 52 months after diagnosis.

BrainChild-03 is enrolling patients ages 1 to 26 years with refractory or recurrent central nervous system (CNS) disease for which there is no available standard therapy; or those with DIPG or diffuse midline glioma who have completed standard therapy.4 Patients must be able to tolerate apheresis or have an available apheresis product; have a life expectancy of 8 weeks or longer; have a Karnofsky or Lansky performance status of at least 60; and have adequate laboratory values and organ function.

Previously reported safety data from BrainChild-03 showed that the most frequently reported adverse effects (AEs) were nausea/vomiting (81%), headache (81%), fatigue (62%), and fever (57%); most AEs were grade 1/2.3 One patient experienced a dose-limiting toxicity of grade 4 intratumoral hemorrhage; this patient was 3 years old and experienced progressive disease between enrollment and initial BCB-276 infusion.

“We are very pleased to now also receive RMAT designation, less than 1 month after being granted breakthrough therapy designation from [the] FDA, for our lead CAR T-cell therapy BCB-276 for the treatment of [patients with] DIPG,” Michael Jensen, MD, founder and chief scientific officer of BrainChild Bio, added in the news release.1 “Receiving designations from 2 independent reviews within [the] FDA further validates the positive CAR T clinical results achieved by our team to date and the urgent need for a treatment for DIPG. Our team is keenly focused on initiating the pivotal phase 2 trial by the end of this year and [looks] forward to continuing to work with the FDA on an accelerated path forward to bring potential new CAR T[-cell] treatments for CNS brain tumors in children and adults.”

References

1. FDA grants regenerative medicine advanced therapy designation for BrainChild Bio’s B7-H3 CAR T-cell therapy for incurable pediatric brain tumors. News release. BrainChild Bio. May 15, 2025. Accessed May 19, 2025. https://brainchildbio.com/wp-content/uploads/2025/05/BrainChild-Bio-RMAT-PR_FINAL.pdf
2. FDA grants breakthrough therapy designation for BrainChild Bio’s B7-H3 CAR T-cell therapy for incurable pediatric brain tumors. News release. BrainChild Bio. April 22, 2025. Accessed April 23, 2025. https://brainchildbio.com/wp-content/uploads/2025/04/BTD-Press-Release_18April2025.pdf
3. 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. 2025;31(3):861-868. doi:10.1038/s41591-024-03451-3
4. Study of B7-H3-specific CAR T cell locoregional immunotherapy for diffuse intrinsic pontine glioma/​diffuse midline glioma and recurrent or refractory pediatric central nervous system tumors. ClinicalTrials.gov. Updated April 25, 2025. Accessed May 19, 2025. https://clinicaltrials.gov/study/NCT04185038