A Study Evaluating Temferon in Patients With Glioblastoma & Unmethylated MGMT

This is a non-randomized, open label, multicenter, phase I/IIa, therapeutic-exploratory, dose escalation, prospective study, involving a single injection of Temferon, an investigational ATMP consisting of autologous CD34+-enriched HSPCs exposed to transduction with a 3rd generation lentiviral vector driving myeloid-specific IFN-alpha2 expression, which will be administered to up to 27 patients affected by GBM who have an unmethylated MGMT promoter. The study will recruit and follow-up patients at a specialist neurosurgical and neuro-oncology units in Italy. Administration of Temferon and hematological follow up will take place at specialist hematology and bone marrow transplantation units.

Potentially eligible patients will be identified immediately after surgical resection of GBM once the MGMT promoter methylator status is known. Once written, informed consent is obtained, and screening procedures have been completed, harvesting of HSPCs will occur. A standard of care regimen lasting approximately 6 weeks, will then take place . During this time, Temferon manufacturing will occur. Following completion of radiotherapy, patients will be admitted for receipt of a conditioning regimen consisting of BCNU and thiotepa (Cohorts 1-6), busulfan and thiotepa (Cohort 5), or busulfan (Cohorts 7 and 8). This will be followed by administration of Temferon. In-patient monitoring will occur until hematological recovery occurs. Thereafter, regular follow-up of patients will occur up to 2 years (+720 days) with the majority of assessments and procedures. At the +720 day visit, patients will be invited to participate in a long term follow-up study which will last for an additional 6 years.

In Part A of the study, 8 cohorts of 3 patients will receive 5 escalating doses of Temferon. On completion of dose escalation in Part A, a conditioning regimen and single dose of Temferon will be selected to be studied in up to a further 6 patients.

In the event that GBM disease progression occurs, patients will be managed with second line therapies including second surgery, TMZ, BCNU, fotemustine or any other approved therapy for GBM.