New drug shows promise against aggressive cancers
A new phase I/II open-label, dose-escalation trial has recently tested the effectiveness of a “Trojan horse” drug in treating multiple types of otherwise treatment-resistant cancer in its late stages.
Recently, a team of experts from The Institute of Cancer Research in London and The Royal Marsden NHS Foundation Trust — both in the United Kingdom — has conducted a phase I/II clinical trial of a newly developed anticancer drug called tisotumab vedotin (TV).To make the novel compound, scientists attached a toxic substance to an antibody that targets the “tissue factor” receptor, a protein that is abundant on the surface of numerous cancer cells and the presence of which predicts poor survival rates.
TV acts by concealing the toxic agent to allow it to enter cancer cells and then releasing the substance within these cells.“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,” explains study author Prof. Johann de Bono.
The researchers conducted this clinical trial in an initial cohort of 27 participants to establish whether the drug was safe for humans and to gauge the correct dosage.Then, the team recruited an additional 120 individuals. The people who participated in this trial were adults aged 18 years and over who had relapsed, advanced, or metastatic cancer.
The types of cancer that the participants had included ovarian, cervical, endometrial, bladder, prostate, and esophageal cancer, as well as non-small cell lung cancer.The researchers have now published their findings in the journal The Lancet Oncology. They note that their trial received funding from two biotech companies: Genmab and Seattle Genetics.
Most of the study participants, who received treatment at 21 different clinics in the United States and Europe, had previously undergone treatment with an average of three other types of drug and developed resistance to all of them.After administering TV to the participants, the researchers found that a significant minority responded well to this new drug, experiencing either tumor shrinkage or an end to tumor growth.
More specifically, 27 percent of the participants with bladder cancer saw an improvement, as well as 26.5 percent of those with cervical cancer, 14 percent of those with ovarian cancer, 13 percent of the participants with esophageal cancer, 13 percent of the individuals with non-small cell lung cancer, and 7 percent of those with endometrial cancer.However, none of the individuals with prostate cancer responded to the new treatment under trial.Among the people who did respond to TV, this outcome lasted 5.7 months on average and up to 9.5 months in some.
As for side effects, the investigators recorded that some participants experienced nosebleeds, fatigue, nausea, and eye problems. However, halfway through the clinical trial, the team was able to modify the intervention protocol to minimize the likelihood of eye problems.The researchers are now testing the effectiveness of TV in other types of cancer, such as bowel cancer, pancreatic cancer, and squamous cell carcinoma of the head and neck. They are also testing the drug in a phase II clinical trial as a second-line treatment for cervical cancer tumors that do not respond to initial therapy.
“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 pretreated with other drugs and who had run out of other options,” says Prof. de Bono.The investigators are now also analyzing biopsy samples that they collected from the participants at the start of the current trial, in the hope that they will be able to find a marker that will help them identify other individuals who are likely to respond well to TV.
“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,” de Bono notes.Prof. Paul Workman, who is chief executive of The Institute of Cancer Research and did not have direct involvement in this study, also emphasizes the importance of a new drug, such as TV, for improving the prognosis of advanced and aggressive cancers.
“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.”
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