Intracerebroventricular B7-H3-targeting CAR T cells for non-pontine DMG and recurrent/refractory pediatric CNS tumors: a phase 1 trial.
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Ronsley Rebecca, Huang Wenjun, Rohlf Ethan, Seidel Kristy, Brown Christopher, Beebe Adam, Rawlings-Rhea Stephanie D, Lindgren Catherine, Sad Tiffany, Crotty Erin E, Leary Sarah E S, Thomsen Alison, Beckstrom Amy R, Holtzclaw Susan L, Hoeppner Corrine, Hurst Diana, MacQuivey Matthew, Goldstein Hannah E, Browd Samuel R, Hauptman Jason S, Lee Amy, Ojemann Jeffrey G, Wright Jason N, Albert Catherine M, Pinto Navin, Gustafson Joshua A, Ho On, Pattabhi Sowmya, Summers Corinne, Annesley Colleen, Wendler Jason N, Gust Juliane, Gardner Rebecca A, Park Julie R, Jensen Michael C, Vitanza Nicholas A
Аннотация
METHODS: BrainChild-03 (NCT04185038) is a single-center, dose-escalation phase 1 study of repeated intracerebroventricular (ICV) B7-H3 CAR T cells in children and young adults with recurrent/refractory CNS tumors (Arms A, B) and diffuse intrinsic pontine glioma (DIPG, Arm C). Here, we report results from Arm B, in which patients with refractory/relapsed CNS tumors or pre- or post-progression non-pontine diffuse midline glioma (DMG) received repeated ICV infusions. Primary objectives were feasibility and safety/tolerability; secondary objectives included CAR T cell detection, disease response, and survival.
RESULTS: Of 36 enrolled patients (atypical teratoid rhabdoid tumor n = 5, DMG n = 8, embryonal tumor with multilayer rosettes n = 2, ependymoma n = 4, high-grade glioma n = 6, medulloblastoma n = 8, pineoblastoma n = 3), manufacturing was successful for 35 patients, 26 of whom received therapy. Median age was 10 years (range 1-26). Dose escalation from 1 × 107 to 10 × 107 CAR T cells/dose identified this dose as the maximally tolerated dose regimen, with no dose-limiting toxicities observed. Across 181 total doses (median 7/patient), common adverse events included headache (n = 26), fever (n = 15), and nausea (n = 14). Median survival from first infusion was 11.5 months, ranging from 3.2 months (pineoblastoma, HGG) to 21.4 months (ependymoma); two patients achieved a partial response.
CONCLUSIONS: Repeated ICV B7-H3 CAR T cell dosing is feasible and tolerable across a spectrum of pediatric CNS tumors, supporting continued investigation in future trials.