TIP-25. Randomized phase 2 clinical trial of repeated intratumoral and cervical perilymphatic injections (CPLIs) of lerapolturev vs. lomustine in recurrent glioblastoma (rGBM): safety lead-in results

BACKGROUND Lerapolturev is a modified, non-pathogenic version of the Sabin™ type 1 poliovirus vaccine that infects myeloid compartments within the tumor microenvironment to generate antitumor immunity by stimulating tumor antigen cross-presentation, dendritic cell homing to lymph nodes, and priming of CD8+ T cells in glioma models. This immunity can be boosted by repeated perilymphatic lerapolturev injections near tumor-draining lymph nodes. Prior clinical trials (NCT01491893, NCT02986178) assessing lerapolturev administered as a single convection-enhanced delivery (CED) infusion into contrast-enhancing recurrent tumor demonstrated a favorable safety profile and improved survival in a subgroup of patients. To overcome factors limiting efficacy in prior trials, we initiated an assessment of repeated lerapolturev CED infusions into residual non-enhancing disease post-resection followed by subcutaneous CPLIs in patients with rGBM (NCT06177964). We are reporting on the safety lead-in. METHODS Eligible patients have solitary supratentorial rGBM amenable to maximal safe resection with KPS ≥70%. During the safety lead-in, patients underwent resection of enhancing tumor followed by two CED infusions of lerapolturev four days apart into residual non-enhancing disease using one of two manufactured lots [3 patients on original lot L1402001 (National Cancer Institute; individual dose: 2x108 TCID50, total dose: 4x108 TCID50) and 3 patients on current lot (Batch SB0301G011, Fujifilm Diosynth Biotechnologies Texas, individual dose: 6x107 TCID50, total dose: 1.2x108 TCID50)]. RESULTS As of June 6, 2025, 6 patients have enrolled. Five patients received repeated lerapolturev CED infusions (1 awaiting infusion). No study-related dose-limiting or unacceptable toxicities were observed. Adverse events possibly, probably, or definitely related to lerapolturev include grade 2 headache (n=2) and grade 1 cognitive disturbance (n=2), vision changes (n=1), nausea (n=1), fatigue (n=1), and pyramidal tract syndrome (n=1). No early difference in adverse events due to lot received was observed. CONCLUSIONS Repeated lerapolturev CED infusions into residual non-enhancing disease post-resection shows an acceptable toxicity profile. Safety and efficacy will be updated.