New ‘Trojan horse’ drug kills cancer from inside

A brand new type of cancer drug that acts as a 'Trojan horse' to get inside tumour cells has shown promise in patients with six different cancer types.

The innovative new drug, called tisotumab vedotin (TV), releases a toxic substance to kill cancer cells from within.
The results, published in The Lancet Oncology, are so positive the drug has now moved forward to phase II trials in cervical cancer and will be tested in a range of additional solid tumour cancers. The researchers led a global clinical trial of nearly 150 patients with a variety of cancer types who had stopped responding to standard treatments. They found that a significant minority of cancer patients responded to the drug, with their tumours either shrinking or stopping growing.

The researchers saw responses in 27 per cent of patients with bladder cancer, 26.5 per cent with cervical cancer, 14 per cent ovarian cancer, 13 per cent with oesophageal, 13 per cent with non-small cell lung and seven per cent with endometrial cancer.

Responses lasted an average of 5.7 months, and up to 9.5 months in some patients, researchers said. TV is made up of a toxic drug attached to the tail end of an antibody. It is designed to seek out a receptor called ’tissue factor’ — present at high levels on the surface of many cancer cells and linked with worse survival. Binding to tissue factor draws the drug inside cancer cells, where it can kill them from within.

The trial initially recruited 27 patients to assess safety and establish the right dose, before expanding to a further 120 patients primarily to look at whether the drug was hitting the right target but also at what effect it had on tumours.
The majority of patients in the early trial had advanced stage cancer (spread locally or around the body) that had already been treated with, and became resistant to, an average of three different types of treatment. TV is now being trialled in other cancer types including bowel, pancreatic, squamous cell lung and head and neck, as well as in a phase II trial as a second-line treatment for cervical cancer.

“What is so exciting about this treatment is that its mechanism of action is completely novel — it acts like a Trojan horse to sneak into cancer cells and kill them from the inside,” said Professor Johann de Bono, a professor at the Institute of Cancer Research. “Our early study shows that it has the potential to treat a large number of different types of cancer, and particularly some of those with very poor survival rates,” de Bono said.

“TV has manageable side effects, and we saw some good responses in the patients in our trial, all of whom had late-stage cancer that had been heavily pre-treated with other drugs and who had run out of other options,” he said.

The researchers have already begun additional trials of the drug in different tumour types and as a second-line treatment for cervical cancer, where response rates were particularly high. They are also developing a test to pick out the patients most likely to respond.

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