MDB-27. phase Ib Clinical Trial Assessing Safety, Tolerability, and Preliminary Efficacy of Alocelyvir (Allogeneic Mesenchymal Cells + Oncolytic Adenovirus) in Pediatric Patients With Recurrent/Progressive Meduloblastoma

Background Relapsed medulloblastoma continues to have a grim prognosis despite advances in the biological understanding of this tumor. In recent years, oncolytic adenovirus therapy has emerged as a promising approach for brain tumors. Methods We conducted a Phase Ib clinical trial in patients with recurrent medulloblastoma, using ALOCELYVIR, a combination of allogeneic mesenchymal stem cells carrying an oncolytic adenovirus. ALOCELYVIR was administered as monotherapy in weekly infusions over 8 doses at 0.5x106 cells/kg/dose. MRI was performed at week 10th, and patients with progression were withdrawn from the trial. The primary objective was to evaluate safety. PCR adenovirus in plasma, anti-adenovirus type 5 antibodies, and immune reconstitution were analyzed. Results Six patients, median age 16.5 years (range, 5–18), with disseminated medulloblastoma (M3) were enrolled. Molecular group 4 (3), group 3/4 (1), group 3 (1), and unknown (1). Patients were heavily pretreated before trial enrollment: median of 3 treatment lines (range, 2–6), including MEMMAT in all but one. All patients completed the 8 planned doses of ALOCELYVIR. Adverse events were mild (no grade 3/4/5). Most frequent adverse events were grade 1 fever, asthenia, myalgias, and anorexia. Adenovirus replication was detected in all patients. Despite week 10 MRI-confirmed progression in all patients, 5 patients pursued additional therapies (5 chemotherapy, 1 radiotherapy), achieving 4 partial responses and 1 stable disease. Survival following trial withdrawal was 27 months, 14 months, 12 months, and 2 months respectively, with two patients remaining alive at 20- and 3-months post-trial. Conclusions This Phase Ib trial demonstrates the feasibility and safety of ALOCELYVIR monotherapy in recurrent medulloblastoma. The prolonged survival observed in most patients after initial progression may indicate an immune-mediated response to ALOCELYVIR. These findings underscore the need for further studies in larger clinical trials to fully explore the therapeutic potential of ALOCELYVIR in improving outcomes for these patients.