Investigational CAR T-Cell Therapy BCB-276 Receives FDA Breakthrough Designation for Pediatric Patients With DIPG

BCB-276, an investigational B7-H3-targeting chimeric antigen receptor (CAR) T-cell therapy, was granted breakthrough therapy designation by the FDA for treatment of pediatric patients with diffuse intrinsic pontine glioma (DIPG). The decision was based on favorable data from the phase 1 BrainChild-03 trial (NCT04185038).¹

AI photo of child with brain tumor | Image Credit: © Lila Patel - stock.adobe.com

DIPG is a fatal central nervous system (CNS) brain tumor found on an area of the brainstem called the pons, which has symptoms such as odd eye movements, slurred speech, difficulty swallowing, trouble maintaining balance, and drooping of one side of the face. It can also interfere with nerve functioning, leading to weakness in the extremities. It primarily affects children, with most diagnoses occurring between ages 5 and 7 years, and accounts for approximately 10% to 15% of all pediatric brain tumors. Prognoses for these patients are extremely poor, with fewer than 10% of children surviving 2 years from diagnosis. The cause of DIPG remains unknown.^2,3

The standard of care treatment for DIPG is palliative focal radiation therapy, which yields a median overall survival (OS) of 11 months. Additional treatments can include chemotherapy, corticosteroids for inflammation and brain swelling, and palliative care. However, DIPG is difficult to treat due to the tumor’s location in the brainstem and its ability to spread to nearby healthy tissue. Additionally, the blood-brain barrier can block many drugs from reaching the tumor.¹

B7-H3 is a highly expressed protein on pediatric CNS tumors, leading investigators to evaluate the efficacy and safety of targeting B7-H3 with CAR T-cell therapy. The approach is built upon 2 phase 1 clinical trials delivering intracranial CAR T cells: BrainChild-01 (NCT03500991), which delivered human epidermal growth factor receptor 2-specific CAR T cells, and BrainChild-02 (NCT03638167), which delivered EGFR806-specific CAR T cells. However, these trials excluded patients with DIPG, leading the investigators to develop an investigational B7-H3-targeting CAR therapy for this population.^1,4,5

BrainChild-03 is a single-center, dose-escalation clinical trial of repetitive intracerebroventricular (ICV) dosing of BCB-276 for children with recurrent or refractory CNS tumors and DIPG. The population included a total of 23 pediatric patients who received 253 ICV doses, establishing DR4—the highest planned dose level, escalating to 10 × 10⁷ cells per dose—as the maximally tolerated regimen.¹

Among all treated patients, the median survival was 10.7 months from the first CAR T-cell infusion and 19.8 months from diagnosis. Three patients remained alive at 44, 45, and 52 months after diagnosis. The most common adverse events included headache, fatigue, and fever, with 1 dose-limiting toxicity (intratumoral hemorrhage) during DR2.¹

The findings suggest that B7-H3 CAR T-cell therapy is tolerable in pediatric and young adult patients with DIPG, even with repeated dosing over several years, and may show clinical benefit.¹

“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, founder and chief scientific officer of BrainChild Bio, said in a news release. “This designation is a major milestone for the children and families...with these devastating brain tumors and represents a new paradigm for treating CNS brain tumors in children and adults, including a large number of patients...with glioblastomas and brain metastases.”³

REFERENCES

1. 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 6, 2025. https://clinicaltrials.gov/study/NCT04185038

2. What is DIPG? what is diffuse intrinsic pontine glioma? DIPG.org. Accessed May 6, 2025. https://dipg.org/facts/what-is-dipg/

3. FDA grants breakthrough therapy designation for BrainChild Bio’s B7-H3 CAR T-cell therapy for incurable pediatric brain tumors. Business Wire. April 22, 2025. Accessed May 6, 2025. https://www.businesswire.com/news/home/20250422418430/en/FDA-Grants-Breakthrough-Therapy-Designation-for-BrainChild-Bios-B7-H3-CAR-T-Cell-Therapy-for-Incurable-Pediatric-Brain-Tumors

4. HER2-specific CAR T cell locoregional immunotherapy for HER2-positive recurrent/​refractory pediatric CNS tumors. ClinicalTrials.gov. Updated December 11, 2024. Accessed May 6, 2025. https://clinicaltrials.gov/study/NCT03500991

5. EGFR806-specific CAR T cell locoregional immunotherapy for EGFR-positive recurrent or refractory pediatric CNS tumors. ClinicalTrials.gov. Updated December 11, 2024. Accessed May 6, 2025. https://clinicaltrials.gov/study/NCT03638167