CTIM-24. AUTOLOGOUS CD34+ ENRICHED HEMATOPOIETIC PROGENITOR CELLS GENETICALLY MODIFIED FOR HUMAN INTERFERON-α2, ARE WELL TOLERATED & RAPIDLY ENGRAFT IN PATIENTS WITH GLIOBLASTOMA MULTIFORME (TEM-GBM_001 STUDY)

• Published in: Neuro-oncology (Charlottesville, Va.) Va.), 2020-11, Vol.22 (Supplement_2), p.ii38-ii38
• Main Authors: Finocchiaro, Gaetano, Gentner, Bernhard, Eoli, Marica, Francesca, Farina, Anghileri, Elena, Girlanda, Stefania, Carrabba, Matteo, Cuccarini, Valeria, DiMeco, Francesco, Legnani, Federico, Pollo, Bianca, Bruzzone, Maria Grazia, Saini, Marco, Ferroli, Paolo, Capotondo, Alessia, Paterra, Rosina, Garramone, Mariagrazia, Mazzoleni, Stefania, Zambanini, Andrew, Russo, Carlo, Naldini, Luigi, Ciceri, Fabio
• Format: Article
• Language: English
• Subjects: Clinical Trials: Immunologic
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/noaa215.158

GBM with an unmethylated MGMT gene promoter is associated with very poor prognosis. A subset of tumor associated macrophages expressing the angiopoietin receptor Tie2 (TEMs) can be genetically modified for local & tumor restricted release of interferon-α2 (IFN). IFN has antitumor effects, inhibits angiogenesis & modulates the immune system. Temferon consists of autologous HSPCs transduced ex-vivo with an LVV encoding an IFN gene & expression control sequences for TEMs. TEM-GBM is an open-label, Phase I/IIa study (Part A: 3x3x3 dose escalation; Part B: n=12), & Temferon (single dose) is given to patients with first diagnosis of GBM & unmethylated MGMT promoter. Part A 3rd cohort is ongoing & completes dosing in September 2020. Eight patients completed screening; one patient died (disease progression) before Temferon was administered. Six patients received Temferon (3 women, 3 men, mean age 52.3 years). Cohort 1 received Temferon 0.5x106 cells/kg & Cohort 2, 1x106 cells/kg. Neutropenia & thrombocytopenia occurred as expected following conditioning & hematologic recovery (HR) occurred median D+13. Transduced PBMCs were identified by vector copy number (VCN) on myeloid cells at HR & at later timepoints. In general, a dose-ordered increase in VCN was observed (mean VCN D+30 CD14+ Cohort 1: 0.094, cohort 2: 0.125); 1 patient in each cohort had low VCNs. VCN remained detectable up to recent follow up visits (≤ D+180). No dose-limiting toxicities have been reported. Four SAEs occurred in 3 patients who received Temferon (pneumonia, pulmonary embolism, febrile neutropenia, fatigue) but these events were not attributed to Temferon, resolved, & may have been related to the conditioning regimen (carmustine & thiotepa). Disease progression has been confirmed in 3 patients who received Temferon. These preliminary results indicate feasibility of engrafting a pre-determined fraction of Temferon cells in the bone marrow of GBM patients without, so far, causing dose-limiting toxicity.