Novel CAR T Earns FDA RMAT Designation for Incurable Pediatric Brain Tumor
BCB-276 has earned regenerative medicine advanced therapy designation from the FDA in diffuse intrinsic pontine glioma, an incurable pediatric tumor.
US FDA
- The FDA has granted regenerative medicine advanced therapy (RMAT) designation to BCB-276 for the treatment of diffuse intrinsic pontine glioma (DIPG), an incurable pediatric brain tumor.
- BCB-276 is an investigational chimeric antigen receptor (CAR) T-cell therapy targeting B7-H3.
- The therapy is being assessed in the phase 1 BrainChild-03 study (NCT04185038).
BCB-276, a B7-H3-targeting CAR T-cell therapy, has been granted FDA breakthrough therapy designation for the treatment of pediatric DIPG.1
RMAT designation can be granted to cell therapies, therapeutic tissue engineering products, and human cell and tissue products that are intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition.2
“We are very pleased to now also receive RMAT designation, less than one month after being granted breakthrough therapy designation from FDA for our lead CAR T therapy, BCB-276, for the treatment of DIPG. Receiving designations from 2 independent reviews within FDA further validates the positive CAR T clinical results achieved by our team to date and the urgent need for a treatment for DIPG,” stated Michael Jensen, MD, founder and chief scientific officer of BrainChild Bio, in a press release.1
In April 2025, the FDA granted BCB-276 breakthrough therapy designation for the same indication. The breakthrough therapy designation is intended to optimize the development and review of drugs that treat serious conditions where early evidence suggests the treatment may provide a significant improvement over currently available options.3
“Our team is keenly focused on initiating the pivotal phase 2 trial by the end of this year and look forward to continuing to work with the FDA on an accelerated path forward to bring potential new CAR T treatments for [central nervous system (CNS)] brain tumors in children and adults,” Jensen added in the press release.1
BrainChild Bio plans to move forward with a phase 2 multicenter, pivotal registration trial evaluating BCB-276 to support a potential biologics license application. This clinical plan is based on alignment between BrainChild Bio and FDA at a type B meeting in late 2024.
About BrainChild-03
Tumor in brain: © peterschreiber.media - stock.adobe.com
The phase 1 BrainChild-03 trial is enrolling patients between the ages of 1 and 26 years with DIPG, diffuse midline glioma, or refractory/recurrent CNS disease at Seattle Children’s Hospital.4 Patients must have a life expectancy of at least 8 weeks, a Lansky or Karnofsky score of at least 60, adequate organ function, adequate laboratory values, and the ability to tolerate apheresis. Those with primary immunodeficiency, bone marrow failure, another active malignancy, or active severe infection are not eligible for participation in the study.
The study’s primary end points are safety and feasibility, and secondary end points include disease response and distribution of CAR T cells.
Findings were published in Nature Communications in January 2025.5 Here, the median survival from initial CAR T infusion was 10.7 months, and the median survival from diagnosis was 19.8 months. Common reported adverse events included headache, fatigue, and fever. One dose-limiting toxicity of intratumoral hemorrhage was reported at dose level 2 (of 4 total dose levels).
About DIPG and BCB-276
DIPG primarily affects pediatric patients between the ages of 5 and 10, with about 300 cases diagnosed per year.1 The current standard-of-care therapy for DIPG is palliative focal radiation, which has a median overall survival of 11 months from diagnosis.
CAR T-cell therapies like BCB-276 can be administered directly into the tumor bed via a catheter to the cerebrospinal fluid. Additionally, BCB-276 keeps the blood-brain barrier intact and minimizes any on-target, off-tumor toxicities.
