The US Food and Drug Administration (FDA) has provided final comments and proposed a clinical development outline for Oxford BioMedica's TroVax renal cancer drug, following a review of the Phase III TRIST study.
The FDA acknowledged all of the points made by Oxford BioMedica, and has provided a clear path for further development of TroVax in multiple cancer settings. TroVax is a therapeutic cancer vaccine that targets the 5T4 tumour antigen.
The Phase III TRIST study has evaluated TroVax plus standard of care against placebo plus standard of care.
The trial enrolled 733 patients with advanced or metastatic renal cancer that were classified as having a good or intermediate prognosis. Patients were randomised to one of the three standards of care, interleukin-2, interferon-alpha or sunitinib.
Vaccinations were discontinued on 11 July 2008, based on the recommendation of the study's independent Data Safety Monitoring Board (DSMB) that concluded the study would not meet its predefined primary endpoint of an improvement in overall survival.
After the data evaluated by the DSMB was discussed with the FDA, it was agreed that plans to initiate further Phase III trials in colorectal cancer would be paused, pending the FDA's review of additional data from the TRIST study.
Based on the clinical trial, the FDA ruled that confounding factors may have contributed to the increased number of deaths in the TroVax arm at the August cut-off date.
Furthermore, the FDA accepted that there was no evidence of specific adverse events that could attribute the imbalance of deaths to TroVax.
The FDA also noted that the analysis of patients receiving TroVax or placebo in combination with interleukin-2 was encouraging and that, scientifically, it is reasonable to postulate that patients with a better haematological profile might respond more favourably to treatment with a cancer vaccine such as TroVax.