IMMU-09. Interim analysis from BrainChild-03: Seattle Children’s Locoregional B7-H3 CAR T Cell Trial for Children with Recurrent Central Nervous System Tumors and DIPG

BrainChild-03 is a phase 1 clinical trial delivering repeated locoregional 2nd generation B7-H3 CAR T cells with 4-1BB co-stimulation to children with central nervous system (CNS) tumors without lymphodepleting chemotherapy. The primary endpoints are feasibility and safety, with secondary endpoints of disease response and correlatives of CAR T cell activity. There are 3 arms: (A) – weekly delivery into the tumor cavity, (B) – weekly delivery into the lateral ventricle for metastatic disease, (C) – biweekly delivery into the lateral ventricle for diffuse intrinsic pontine glioma (DIPG). In total, 23/24 (96%) enrolled patients have had successful CAR T manufacturing. 16/24 patients are evaluable and have received a total of 141 intracranial CAR T cell doses. Unevaluable patients include 5 never treated and 3 who progressed prior to receiving the minimum doses to become evaluable. The most common adverse events have been headache (16/16, 100%), nausea/vomiting (12/16, 75%), and fever (10/16, 63%). There has been 1 DLT for an intratumoral hemorrhage and no cytokine release syndrome (CRS). 7 evaluable patients with DIPG (Arm C) have received a cumulative 50 infusions. 5/7 DIPG patients enrolled after progression and have a median survival of 246.5 days post-initial CAR T cell infusion, with 4/5 still alive. The 2 DIPG patients enrolled prior to progression had radiographic improvement, including 1 with improvement of a cranial nerve 6 palsy who self-withdrew from protocol therapy after 18 infusions over 12 months and 1 still on protocol therapy after 11 infusions over 6 months. DIPG patients have had increased CSF levels of proinflammatory mediators (e.g. CXCL10, CCL2, IFNg, GM-CSF, IL-12) without systemic cytokine changes. 5/7 DIPG patients had detectable CAR T cells in their CSF post-infusion. Ultimately, the preliminary experience suggests locoregional delivery of B7-H3 CAR T cells may be feasible and tolerable in children with CNS tumors, including DIPG.