ICR unveils efficacious cancer drug with new mechanism of action

Researchers from the Institute of Cancer Research (ICR) and the Royal Marsden NHS Foundation Trust have announced promising results from a phase I/II into tisotumab vedotin (TV) in patients with one of six, drug-resistant cancers.

TV is attached to an antibody, which has been designed to seek out the tissue factor receptor present in large amounts on cancer cells linked with worst patient survival. When the antibody attaches to the receptor, it is drawn into the cancer cell, TV then releases a toxic substance to kill the cancer cells from within.

Across the six cancer types, ovary, cervical, endometrial, bladder, prostate, oesophagus, squamous cell carcinoma in the neck and head and non-small cell lung cancer (NSCLC), 15.6% participants had an objective response to the drug, which was defined as tumours shrinking or not growing.

Bladder cancer had the best response with 27%, followed by cervical cancer with 26.5%, ovarian cancer with 14%, oesophageal cancer and NSCLC both with 13%, and 7% for endometrial cancers.

ICR Regius professor of cancer research Professor Johann de Bono said: "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. 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."

The InnovaTV study initially recruited 27 participants to assess the safety and establish the right dose of the drug between 2013 and 2015. Then it was expanded to 147 patients between 2015 and 2018.

As a result of these positive results, TV is being investigated in other cancers, such as bowel, squamous lung cancer, as well as being progressed into phase II for cervical cancer.

De Bono said: "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."

ICR chief executive Professor Paul Workman said: "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."

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