The purpose of this clinical trial is to evaluate the survival of patients with non-operable, progressive and/or recurrent glioblastoma multiforme (GBM) treated with Tf-CRM107 compared to patients treated with a number of presently used chemotherapeutic agents, such as temozolomide and procarbazine. These chemotherapeutic agents are regarded as the best standard of care (BSC) currently available to patients. This is an open-labelled study which will enrol up to 323 patients randomised in a 2:1 ratio of Tf-CRM107 to BSC across 21 sites in the United States, 25 in Europe and four in Israel.

WHAT IS TF-CRM107 AND HOW DOES IT WORK?
Tf-CRM107 is an adapted diphtheria toxin joined to human transferrin. The diphtheria toxin gains entry to the tumour cell when the transferrin to which it is attached binds to transferrin receptors on the surface of the tumour cell. Transferrin receptors are particularly prevalent on rapidly dividing cells due to their need for an increased intake of iron to facilitate growth. The high-level of transferrin receptor expression on glioma cells makes it an ideal target in the treatment of brain tumours. Once inside the cell, the diphtheria toxin interferes with the ability of the cell to synthesise proteins by interfering with elongation factor 2 (EF-2), which ultimately kills the cancer cell.

HOW THE DRUG IS ADMINISTERED - CONVECTION ENHANCED DELIVERY (CED)
Tf-CRM107 is pumped directly into the brain tumour via two catheters using the technique of Convection Enhanced Delivery (CED), which was developed at the National Institutes of Health (NIH) in the United States. CED allows Tf-CRM107 to be distributed throughout the tumour. This also circumvents the usual obstacles present in drug delivery to the brain caused by the blood-brain barrier.