TIP-21. Phase I trial of mesenchymal stem cells carrying Delta-24-RGD given intraarterially in recurrent glioma: Early report

Abstract Delta-24-RGD (D24) is a tumor-selective oncolytic adenovirus that has shown promise in several early-stage trials. However, the intra-tumoral injections used in these trials fail to deliver D24 in approximately 45% of cases (Lang et al.,2018). To improve delivery, we developed a novel strategy in which D24 is loaded into tumor-homing mesenchymal stem cells (MSCs) and the resulting MSC-D24 are administered via endovascular selective intra-arterial (ESIA) injection. To assess the feasibility, safety and efficacy of MSC-D24 in patients with recurrent glioma, we undertook a Phase 1 dose-escalation trial of MSC-D24 administered via ESIA injection in patients with recurrent high-grade glioma. Dose (cell number) was escalated in a planned six cohorts; primary and secondary outcomes were adverse events and survival, respectively. To date we have enrolled 17 patients, nearly completing escalation to dose-level 5 (2x108 cells/20 ml). Median age is 52 years; 16 patients had IDH-wild type glioblastomas. Femoral access was used in six cases and radial access in eleven. Cells were injected into the posterior cerebral artery (P2: 3 cases; P3: 3 cases), middle cerebral artery (M1: 2 cases; M2: 5 cases), anterior cerebral artery (A2: 4 cases). There were no strokes or other toxicities based on post-injection angiogram, MRI (DWI), or clinical exam. Five patients (29%) survived >2 years, and two patient are still alive (> 4 years), one with a complete response. In this first-in-human trial, ESIA injections of MSC-D24 are feasible and safe, resulting in long-term survival in a subset of patients. Next steps are to complete enrollment in cohort 6 (multiple injections) and assess biological effects in a window-of-opportunity arm.