Novel CAR T Therapy Earns FDA Breakthrough Status for Incurable Pediatric Brain Tumor

• The FDA has granted breakthrough therapy 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

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.²

“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,” said Michael Jensen, MD, founder and chief scientific officer of BrainChild Bio, in a press release.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 (CNS)] brain tumors in children and adults, including a large number of patients suffering with glioblastomas and brain metastases."

3D illustration of brain anatomy: © PIC4U - stock.adobe.com

BCB-276 is being assessed in the phase 1 BrainChild-03 study, and BrainChild Bio plans to advance the agent to a phase 2, multicenter, registrational study.

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.

About BrainChild-03

The phase 1 BrainChild-03 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.³ 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.

The study has an estimated primary completion date of May 2026.

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 22, 2025. https://tinyurl.com/bddbsc3p

2. Breakthrough therapy. US FDA. Updated January 4, 2018. Accessed April 22, 2025. https://tinyurl.com/c4wwz4ux

3. 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 December 11, 2024. Accessed April 22, 2025. https://clinicaltrials.gov/study/NCT04185038