DIPG-81. PHASE IB CLINICAL TRIAL ASSESSING SAFETY, TOLERABILITY, AND PRELIMINARY EFFICACY OF ALOCELYVIR (ALLOGENEIC MESENCHYMAL CELLS + ONCOLYTIC ADENOVIRUS) COMBINED WITH RADIOTHERAPY IN PEDIATRIC PATIENTS WITH NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)

Abstract

Abstract BACKGROUND Despite recent advances in our understanding of biology, pediatric patients diagnosed with diffuse intrinsic pontine glioma (DIPG) still face a bleak prognosis. In recent years, oncolytic adenovirus therapy has emerged as a promising approach in cancer treatment. METHODS We conducted a phase Ib clinical trial in patients newly diagnosed with DIPG, utilizing ALOCELYVIR, an advanced therapy medicine that combines allogeneic mesenchymal stem cells carrying an oncolytic adenovirus. ALOCELYVIR was administered as weekly intravenously infusions from the first week of radiation for 8 doses, at a dose of 0.5x106 cells/kg/dose. The primary objective was to assess the safety of combining ALOCELYVIR with radiotherapy in patients with newly diagnosed DIPG. PCR analysis of adenovirus in plasma, anti-adenovirus type 5 antibodies, and immune reconstitution were analyzed. RESULTS A total of 6 patients, aged 5 to 15 years, were recruited. Four patients underwent biopsy, confirming an H3K27-mutated DIPG. All patients except one completed the trial; this patient progressed during radiotherapy, and after the fifth dose of ALOCELYVIR. Adenovirus replication in plasma was observed in four patients. Median OS was 11.5 months (range, 3-25), and median PFS was 7.5 months (range, 2-13). One patient is still alive 25 months after diagnosis. Adverse events among patients were all mild, including fever, asthenia, vomiting, headache, and myalgias, all grade I. Clinical and radiological pseudoprogression were documented in four patients, necessitating the addition of steroids +/- bevacizumab as anti-inflammatory treatment. CONCLUSIONS Our phase Ib clinical trial demonstrates the feasibility and safety of combining ALOCELYVIR with radiotherapy in pediatric patients newly diagnosed with DIPG. Furthermore, the manageable adverse event profile observed underscores the potential of ALOCELYVIR as a therapeutic option for DIPG. These findings warrant further investigation through larger clinical trials to elucidate the full therapeutic potential of ALOCELYVIR in improving outcomes for pediatric patients with DIPG.