CTIM-24. SAFETY, EFFICACY, AND GENETIC PROFILING OF JL15003 IN RECURRENT GLIOBLASTOMA: A SINGLE-ARM OPEN-LABEL PHASE I CLINICAL TRIAL

Abstract The oncolytic virus (OV) therapies against recurrent glioblastoma (rGBM) have been shown the promising clinical outcomes with good safety and extended overall survival. However, the genetic profile of OV therapy in rGBM is not clear yet. Here, we report the phase I clinical trial and genetic profiling results of JL15003, a recombinant poliovirus inChinese patients with rGBM. The primary endpoint was the safety with the determination of MTD and/or RP2D. The secondary endpoint was the efficacy evaluation by iRANO. The dose escalation started from a low dose titration at 1 × 106 CCID50 of single dose JL15003 and then followed the standard “3 + 3” designed dose escalation at doses 5 × 106CCID50, 2 × 107 CCID50, and 8 × 107 CCID50. Total 17 patients were involved in this study and received a single dose administration of JL15003. JL15003 was well tolerated and no dose-limiting toxicities (DLTs) were observed until the highest dose (expansion dose) of 8x107 CCID50. No ≥Grade 3 treatment-related adverse event (TRAE) occurred. The most common TRAE (≥10%) were cerebral edema(11.8%). Median overall survival among the patients who received JL15003 was 19.4 months (as of 27 Mar, 2025). Among the 17 patients, 1 patient was complete response, 2 patient waspartial response and 8 patients were stable disease based on iRANO. Genetic profile demonstrates that JL15003 exhibits in tumor tissue no more than four months, with the therapeutic efficacy strongly associated with glioblastoma cellular states (NPC-like, OPC-like, MES-like, and AC-like). Complementary analyses revealed peritumoral microglia may potentiate anti-tumor immunity through enhanced antigen presentation, indicating a dual role of neural microenvironment components in modulating therapeutic outcomes. The study demonstrates that JL15003 is safe and well tolerated in patients with rGBM and the preliminary efficacy has been shown. In addition, the genetic profiling by single cell seq and RNA Seq provides the data for mechanism analysis and proposes the multi-dose administration of JL15003 and the biomarkers for next trial design in patients with rGBM.