Oxford BioMedica has received ethical approval from the UK Gene Therapy Advisory Committee for TroVax to enter a Phase II clinical trial in patients receiving chemotherapy for colorectal cancer
The trial is planned to start within two months.
TroVax is designed to stimulate a patient's immune system to recognise and destroy cancer cells.
The product is based on a gene that encodes a protein, known as 5T4, which exists only on the surface of tumour cells and not on normal cells.
When this gene is expressed by Oxford BioMedica's highly engineered virus-based delivery system, it induces a potent anti-tumour response.
This means that cells and antibodies of the immune system seek out the tumour cells carrying 5T4 and destroy them.
TroVax has successfully completed a Phase I/II trial in metastatic colorectal cancer patients and has been shown to be safe and well tolerated in these patients.
Furthermore, TroVax was shown to be immunogenic, inducing anti-5T4 antibodies and T-cells in 11 out of 12 patients.
In addition disease stabilisation, reduction in circulating tumour markers and tumour necrosis was observed in some patients.
These data form the basis for moving into Phase II.
The Phase II programme is designed to maximise the speed with which TroVax could reach a cancer market of reasonable size.
The strategy is to continue to focus on colorectal cancer and to move quickly towards making TroVax ready for a Phase III efficacy study.
The target population will not be the very late stage, post-chemotherapy group of the first trial but rather the somewhat earlier patient population receiving chemotherapy for the first time for metastatic or inoperable disease.
The rationale is that TroVax might contribute to tumour reduction via immune system-mediated cell killing and this could be amplified in the presence of the cell death that is induced by chemotherapy.
This would place TroVax alongside current first-line chemotherapy and provide a relatively simple, relatively short-term survival, or time-to-progression, end-point.
In order to get to a Phase III study in combination with chemotherapy, a short Phase II study is required to show that TroVax induces an appropriate anti-5T4 response in this context.
It is this study that has been approved by GTAC.
GTAC has approved an open label Phase II trial in up to 15 patients of 5 doses of TroVax in patients receiving 5-fluorouracil, leukovorin and irinotecan.
The end-points of the trial will be the immune response to TroVax and safety in conjunction with this chemotherapy.
Therefore the trial is expected to last only 6 months after the recruitment of the last patient.
The company anticipates rapid recruitment because of the large number of patients fulfilling the entry criteria.
The protocol is designed to give immunological readouts following vaccination before, during and just after completion of chemotherapy.
The trials will take place at the Christie Hospital in Manchester and two other centres in the UK.
The overall aim is to provide data to finalise the design of a Phase III protocol that could lead to product registration in 2007/8.
If TroVax is successful in this context and achieves product registration for use in colorectal cancer patients receiving first line chemotherapy, it could command a market of between $0.5-1.0 billion.
Commenting on GTAC's approval chief executive, Alan Kingsman said " TroVax is an exciting product and it is very pleasing to see it progressing towards the market.
"Making TroVax a potential phase III product for 2004 should potentiate our ability to find the right partner for this product.
"The company is also seeking approval for trials to study the use of TroVax for other cancers as part of the strategy to broaden the market potential of the product."
