PL02.1.A LOCOREGIONAL BI-SPECIFIC CAR-T CELLS TARGETING CD44 AND CD133 IN RECURRENT GLIOBLASTOMA: THE INTERIM RESULTS OF THE FIRST IN-HUMAN CLINICAL TRIAL

Abstract BACKGROUND Recurrent glioblastoma (rGBM) remains no standard of care exists, with a median overall survival of less than 1 year. Here, we report the pre-clinical data and the first four patients with rGBM in a phase I study of locoregionally administration of newly developed tandem CAR-T cell, targeting CD44 and CD133, armored with a truncated IL7Ra intracellular domain (Tris-CAR-T). MATERIAL AND METHODS The primary outcomes were safety and any adverse events associated with Tris-CAR-T administration. Secondary outcomes include the distribution and persistence of Tris-CAR-T cells, cytokine concentration, and the therapeutic effect according to immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria. At present, six patients of newly diagnosed rGBM underwent different doses of Tris-CAR-T administration via Ommaya reservoir of intratumoral or ventricular implantation. The first two patients had single or multi-doses of 107 Tris-CAR-T cells, the third and fourth patients had multiple doses of 108 Tris-CAR-T cells, and the last 2 patients had weekly doses of 0.5x108 Tris-CAR-T cells administration. Cytokine release syndrome and other side effects were assessed via cytokine quantification (serum and cerebrospinal fluid), K-CRP, and body temperature. Specimens of peripheral blood, cerebrospinal fluid, CAR-T products were collected for further bioinformatics analysis. RESULTS No neurotoxicity or adverse event greater than grade 1 was observed until now. Radiographic response and improvement in symptoms and signs were observed within days after the first infusion, and continued in the follow-up. Some patients underwent a remarkable tumor regression. CONCLUSION The newly constructed Tris-CAR-T cells are capable of GBM suppression with limited side effects. Long-term tumor control is considered to be related to dosage, product quality, and intervention frequency. A weekly or biweekly administration might be considered. The inspiring clinical response needs to be strengthened by follow-up and investigations in biological specimens (ClinicalTrials.gov identifier: NCT05577091)