A new type of cancer drug that acts as a "Trojan Horse" getting inside tumor cells has shown some promising results in patients with advanced drug-resistant cancers.
Patients with six different cancer types, have responded positively to the new treatment.This includes those with cervical, bladder, ovarian and lung tumors.The promising new drug is called tisotumab vedotin (or TV for short). This innovative drug releases a toxic substance that would kill cancer cells from within. Due to its positive results, it already moved forward to phase II trials for patients with cervical cancer and also will be tested in a range of solid tumor cancers.
A phase I/II global clinical trial of about 150 European patients with cancer whose body stopped responding to standard treatments was led by a team at the Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust.
The study was published in The Lancet Oncology and funded by Genmab and Seattle Genetics.
There are responses in 27% of patients with bladder cancer, 26.5% for cervical cancer, 14% for ovarian cancer, 13% with esophageal, 13% with non-small cell lung, and 7% with endometrial cancer (although not in any men with prostate cancer).
In some patients, responses lasted an average of 5.7 months, and up to 9.5 months. There are sideeffects reported in the study and that is nose bleeds, fatigue, nausea and eye problems. Halfway of the trial researchers adjusted the protocol to reduce eye-related side effets.
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The drug (TV) is made up of a toxic drug that is attached to the tail end of an antibody. Antibody is designd to find out a receptor called "tissue factor" - this are present at high levels on the surface of various cancer cells and linked with worse survival rates. The tissue binding factor draws the drug inside cancer cells, then it can kill them from within.
Initial number of patients recruited is 27 and was later on expanded to 120 patients primarily to look at whether the drug was hitting the right target but also to examine its effects on tumors.
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.
“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 from The Institute of Cancer Research, London.
“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.
“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 tumor 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.”
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.
Biopsy samples taken at the start of the trial are currently being analyzed for expression of tissue factor on tumor cells to see if it could be used as a marker to select patients most likely to respond to the drug.
Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said: “We’ve seen major advances against cancer in recent decades, but many tumor 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 tumors that have become resistant to standard therapies.
“It’s 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.”
Source: www.icr.ac.uk
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