Revolutionary ‘Trojan horse’ drug has successfully treated British patients with six different forms of cancer

A revolutionary ‘Trojan horse’ drug has successfully treated British patients with six different forms of cancer, scientists have revealed.

It is hoped the jab may help cure, or at least prolong the lives, of people with some of the most common and lethal tumours – within five years.

It hides a toxic chemical inside an antibody in order to sneak it inside a tumour and attack it from within.

More than a quarter of cervical and bladder cancer patients responded even though their illness was well advanced and considered untreatable.

The new therapy, administered intravenously, also worked against ovarian, lung, gullet and womb tumours, reports the team.

A bigger trial involving hundreds of patients with other types of cancer is already underway owing to the “early promise”.

Study leader Professor Johann de Bono, of The Institute of Cancer Research, London, said this includes tumours of the bowel, pancreas, head and neck.

He said: “What is so exciting about this treatment is its mechanism of action is completely novel – it acts like a Trojan horse to sneak into cancer cells and kill them from the inside.

“Our early study shows it has the potential to treat a large number of different types of cancer, and particularly some of those with very poor survival rates.”

Asked if there was a time frame for when this could be a viable option for cancer patients in general, Prof de Bono replied: “Five years or less.”

Called tisotumab vedotin, or ‘TV’ for short, it releases a poisonous substance deep inside the tumour that kills the cancer cells.

The preliminary global trial included almost 150 patients from the UK, the US, Belgium, Denmark and Sweden.

They had a variety of cancers that had either spread locally or to other organs and become resistant to standard drugs.

Prof de Bono, also a consultant oncologist at The Royal Marsden NHS Foundation Trust, said a significant minority found their tumours “either shrinking or stopping growing.”

This included 27 and 26.5 percent of those with bladder or cervical cancer, respectively, and 14 per cent with ovarian cancer.

The same occurred among 13 per cent of those with oesophageal or the most common form of lung cancer, known as non-small cell.

The results were so good the drug will now be tested in a range of additional solid tumour cancers involving much larger numbers.

Meanwhile, seven per cent of women with endometrial cancer, that begins in the lining of the womb, also responded. It was ineffective against prostate cancer.

The study published in The Lancet Oncology found responses lasted an average of almost six months – and up to nine and a half months in some patients.

TV is made up of a toxic drug attached to the tail end of an antibody. The antibody is designed to seek out a receptor called ’tissue factor’.

This is present at high levels on the surface of many cancers cells and linked with worse survival.

Binding to tissue factor draws the drug inside cancer cells – where it kills them from within.

The trial initially recruited 27 patients to assess safety and establish the right dose, before expanding to a further 120 patients.

This was mainly to look at whether the drug was hitting the right target, but also at what effect it had on tumours.

Most patients in the early trial had advanced stage cancer that had spread locally or around the body.

They had already been treated with, and became resistant to, an average of three different types of treatment.

Prof 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.

“We have already begun additional trials of this new drug in different tumour types and as a second-line treatment for cervical cancer, where response rates were particularly high.

“We are also developing a test to pick out the patients most likely to respond.”

The main side effects were nose bleeds, fatigue, nausea and eye problems. Halfway through the trial the researchers adjusted the protocol to reduce the latter.

Prof Paul Workman, chief executive of The Institute of Cancer Research, said: “We have seen major advances against cancer in recent decades.

“But many tumour types remain very difficult to treat once the cancer has begun to spread.

“We desperately need innovative treatments like this one that can attack cancers in brand new ways, and remain effective even against tumours that have become resistant to standard therapies.

“It is exciting to see the potential shown by TV across a range of hard-to-treat cancers. I look forward to seeing it progress in the clinic and hope it can benefit patients who currently have run out of treatment options.”

The price has not yet been set. This will be worked out based on the success of the drug, the number of cancers it treats and what individual markets can bear.

Patients can access the drug before it is given NHS approval via clinical trials if they meet the eligibility criteria.

Biopsy samples taken at the start of the trial are currently being analysed for expression of tissue factor on tumour cells to see if it could be used as a marker to select patients most likely to respond to the drug.

Prof de Bono said work is ongoing to discover the potential mechanism behind the success of the drug against so many different types of tumour.

The study was funded by Danish and US biotech companies Genmab and Seattle Genetics, respectively,

By Mark Waghorn

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