The MODULATE study, led by Prof Niall Tebbutt, is investigating the effectiveness, safety and tolerability of nivolumab with either BBI-608 or BNC105 for patients with metastatic colorectal cancer – an experimental strategy aiming to stimulate the immune system to attack the cancer.
On the significance of the study, Prof Tebbutt says, ‘This is an important and exciting study for the group as it is represents the first study of immunotherapy undertaken by GI Cancer Institute.’
This study has recruited 72 out of a total of 90 participants since its opening in September 2018, and it is expected recruitment will be completed by early 2020.
Nivolumab is an antibody (a type of human protein) that can stimulate the immune cells (called lymphocytes) to attack a cancer. This process is known as “immunotherapy”. Nivolumab acts against PD-1 which is a protein in cancers that researchers believe allows cancer to escape the immune system. Nivolumab can stop the cancer cells escaping the immune system and the body’s own immune reaction may help to destroy cancer cells. In order for nivolumab to be effective, immune cells need to infiltrate close to the tumour itself. It has been observed that in many cases of bowel cancer, immune cells do not penetrate near the tumour which may explain why nivolumab given on its own is an ineffective treatment for many patients with bowel cancer. This does not apply to a number of other cancer types.
BBI-608 is a molecule that inhibits cancer stem cells, and particularly the signalling protein STAT3. STAT3 suppresses the immune system and inhibits immune cells getting close to tumour cells. Researchers believe that BBI-608 will allow immune cells to move close to tumour cells and stimulate the immune cells in combination with nivolumab.
The other treatment arm being studied is BNC105, a ‘vascular disrupting agent’. This damages the blood supply of tumour, resulting in tumour damage and inflammation. Researchers believe this could allow immune cells to move close to the tumour and, in combination with nivolumab, stimulate the immune cells.