Children and young adults with recurrent or refractory (R/R) medulloblastoma are in dire need of novel targeted treatment strategies that increase cure rates and diminish treatment-related morbidity. The team at Stanford launched a phase-I clinical trial (NCT07087002) in August 2025 to evaluate the manufacturing feasibility and safety of autologous chimeric antigen receptor (CAR) T cells targeting the oncofetal protein Glypican-2 (GPC2), designed to treat pediatric and young adult patients with confirmed GPC2-positive R/R medulloblastoma or other eligible Central Nervous System (CNS) Embryonal Tumors using intracerebroventricular (ICV) administration.
This study administers sequential intracerebroventricular doses of GPC2-CAR T cells in up to eight cycles using a two-phased Bayesian statistical design employing intrapatient dose escalation. Subjects receive lymphodepleting chemotherapy prior to the initial dose of GPC2-CAR T cells, which can be repeated if the CD4 count recovers to >200 cells/uL and other eligibility criteria are met. To date, they have enrolled four patients and are actively recruiting.
GPC2 is a compelling immune target, that is expressed in the developing brain, yet essentially absent from postnatal normal tissues. This trial builds upon preclinical work on engineering GPC2-CAR T cells tuned towards clinically relevant antigen densities in neuroblastoma (Heitzeneder et. al) and unpublished preclinical studies in orthotopic medulloblastoma xenograft models using locoregional CAR-T delivery. The key aspect of this proposal is to conduct extensive correlative studies and evaluate GPC2-CAR T cell mediated anti-tumor responses and predictors of response, resistance and toxicity with the goal to improve patient outcomes driven by insights gained from translational studies.
Projects and Grants
GPC2-CAR T Cell Therapy for Relapsed or Refractory Medulloblastoma and other CNS Embryonal Tumors in Children and Young Adults
