Brainchild Bio planning pivotal trial of CAR T-cell therapy for DIPG
Positive data should support applications for BCB-276's regulatory approval
Brainchild Bio plans to launch a pivotal Phase 2 clinical trial to test its investigational cell therapy BCB-276 in patients with diffuse intrinsic pontine glioma (DIPG), an aggressive and incurable brain tumor that mainly affects children.
The trial will be registrational, meaning positive data should support applications for the therapy’s regulatory approval. Brainchild Bio recently reached an agreement with the U.S. Food and Drug Administration (FDA) on this accelerated clinical development plan.
Continuing BCB-276’s development is backed by recently published Phase 1 trial data that showed the cell therapy product from which BCB-276 was derived was safe and feasible in children and young adults with DIPG.
“We are very pleased to have a solid path forward for our clinical development of BCB-276 in DIPG, enabling us to continue our progress for children and families struggling with this devastating brain cancer that currently has no approved treatments,” Michael Jensen, MD, founder and chief scientific officer of Brainchild Bio, said in a company press release. “We look forward to continuing to work with the FDA and to generate the additional data required to support a successful IND submission [clinical trial application] leading to the initiation of the BCB-276 pivotal trial by the end of 2025.”
DIPG is an aggressive and fatal type of glioma, a class of brain tumors that form in the support cells of the nervous system, that’s usually diagnosed in children between ages 5-10. DIPG tumors grow in the brainstem, which is involved in controlling critical involuntary body functions like heart rate and breathing, making it difficult to develop effective treatments for DIPG without damaging healthy brain tissue.
There are no therapies specifically approved for DIPG. Standard care generally involves radiation therapy to temporarily shrink the tumor and ease symptoms, but this doesn’t have a lasting impact on survival. Patients survive a median of eight to 11 months from the time they are diagnosed.
Brainchild Bio is a spinoff as a result of efforts at Seattle Children’s Hospital in developing CAR T-cell therapies, which work to better equip the immune system to target and kill tumor cells.
Results of Phase 1 study of BCB-276
BCB-276 is Brainchild Bio’s lead candidate. The treatment involves collecting a patient’s own immune T-cells, which have innate cancer-fighting abilities, and modifying them to contain a chimeric antigen receptor (CAR) that will specifically recognize and target B7-H3, a protein found at high levels on DIPG cells. When the engineered T-cells are infused back into the patient, they’re equipped to launch an attack against B7-H3-expressing tumor cells.
The therapy is delivered directly into the fluid-filled spaces of the brain, a technique called introcerebroventricular (ICV) dosing, via a surgically implanted device. This lets the treatment directly access the area where the tumor resides, but minimize side effects that could occur from systemic exposure. It also enables repeated dosing.
Seattle Children’s is running BrainChild-03 (NCT04185038), a Phase 1 clinical trial to evaluate the feasibility of a B7-H3-targeted CAR T-cell therapy in children and adults, ages 1 to 26, with recurrent or refractory brain tumors and DIPG. It may still be recruiting participants.
Findings from the arm of the trial involving 21 patients who’d received standard radiation therapy at the time of their diagnosis were recently published in Nature Medicine. Twelve were treated with the CAR T-cell therapy after their disease had progressed and nine were treated before any tumor progression had occurred. All received the cell therapy via repeated ICV infusions at one of four escalating dosing regimens. The treatment was administered every other week over two months and additional doses were possible in eligible participants.
The therapy was well tolerated, with the most common side effects that may have been related to treatment including headache, nausea or vomiting, fatigue, and fever, safety analyses showed.
Among all the treated patients, the median time from diagnosis to death was 19.8 months, or a little more than 1.5 years. Patients survived a median of 10.7 months from their first infusion. Three patients who started treatment before their disease progressed were alive as of the last follow-up and had survived for up to 4.5 years after their diagnosis. Two remain on the therapy.
The findings are preliminary, but Brainchild Bio believes they demonstrate B7-H3-targeted CAR T-cell therapy has promise at prolonging survival in DIPG.
“This is a time of strong momentum for the CAR [T-cell] discoveries and clinical trials in pediatric brain cancer,” said Jeff Spring, MD, CEO of Seattle Children’s. “Our innovation model is built to accelerate technology to bring potential cures to kids faster, and it is gratifying to see that Seattle Children’s launch of Brainchild Bio is supporting the advancement of a CAR T therapy to reach children with an incurable brain cancer.”
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