Breakthrough Designation Granted to BCB-276 for Pediatric DIPG

Three patients enrolled in BrainChild-03 were still alive at 44 months, 45 months, and 52 months, respectively, from diagnosis.

BCB-276, an autologous B7-H3–targeted CAR T-cell therapy, has received FDA breakthrough therapy designation for use in pediatric patients with diffuse intrinsic pontine glioma (DIPG).¹

The designation is supported by data from the phase 1 BrainChild-03 trial (NCT04185038), where data demonstrated that evaluable patients with DIPG (n = 21) experienced a median overall survival (OS) of 10.7 months following the infusion of the CAR T-cell therapy and a median OS of 19.8 months from diagnosis.² Notably, 3 patients were still alive at 44 months, 45 months, and 52 months, respectively, from diagnosis.

Regarding safety, 1 dose-limiting toxicity (DLT) of grade 4 intratumoral hemorrhage was reported in a 3-year-old patient who experienced progressive disease between enrollment and initial infusion. The most common adverse effects (AEs) included headache (81%), nausea/vomiting (81%), fatigue (62%) and fever (57%), although most AEs were grade 1 or 2. Study authors noted that fever was considered evidence of local immune activation, rather than cytokine release syndrome (CRS). No instances of immune effector cell–associated neurotoxicity syndrome were reported.

“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, stated in a news 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.”

BrainChild-03 is a phase 1 study being conducted at Seattle Children’s Hospital in Washington, where investigators are enrolling patients 1 to 26 years of age with refractory or recurrent CNS disease without available standard therapy, or with DIPG or diffuse midline glioma at any point following completion of standard therapy.³

Patients need to be able to tolerate apheresis or have an apheresis product available for the manufacturing of BCB-276. Other key inclusion criteria comprise a life expectancy of at least 8 weeks, a Lansky or Karnofsky performance status of at least 60, and adequate organ function and laboratory values.

Patients are being excluded if they have grade 3 or higher cardiac dysfunction or symptomatic arrhythmia requiring intervention; have primary immunodeficiency or bone marrow failure syndrome; have clinical or radiographic evidence of impending herniation; have dysphagia higher than grade 3; have an active malignancy other than the primary CNS tumor; have an active severe infection; or are currently receiving any anticancer agents or chemotherapy.

In arm C, patients with DIPG are receiving BCB-276 without lymphodepletion; the CAR T-cell therapy is administered once every 14 days over 8 weeks during the DLT period.² Eligible patients are allowed to receive additional courses once every 2 to 4 weeks after the DLT period. In patients treated thus far, BCB-276 was given at up to 1 x 10⁷ CAR T cells per dose (n = 3), up to 2.5 x 10⁷ CAR T cells per dose (n = 6), up to 5 x 10⁷ CAR T cells per dose (n = 3) and up to 10 x 10⁷ CAR T cells per dose (n = 6).

Safety and feasibility are serving as the trial’s primary end points.³ Secondary end points include the distribution of B7-H3–expressing CAR T cells, disease response, and biomarkers of antitumor CAR T-cell functionality.

BrainChild Bio, the developer of BCB-276, intends to advance the CAR T-cell therapy to a phase 2, registration-enabling trial that could support filing of a biologics license application to the FDA seeking the approval of BCB-276 for the treatment of pediatric and young adult patients with DIPG.¹ The company and the FDA aligned on a plan to proceed in a meeting in 2024.

“[Breakthrough therapy] designation is an important milestone for Seattle Children’s and demonstrates our continued momentum in pediatric brain cancer research,” s. Jeff Sperring, MD, chief executive officer of Seattle Children’s Hospital, added in a news release. “We harness the power of research to bring potential cures to kids faster, and we’re excited by the early promise shown by our work with BrainChild Bio to advance a potential CAR T[-cell] therapy.”

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. April 22, 2025. Accessed April 23, 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. 2025;31(3):861-868. doi:10.1038/s41591-024-03451-3
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 23, 2025. https://clinicaltrials.gov/study/NCT04185038