The findings of a phase 1 trial examining a medication mixture targeting multiple mutant variants of cancer’s ‘death star’ protein have been released by the Institute of Cancer Research (ICR) in London and The Royal Marsden NHS Foundation Trust.
In an early-phase clinical trial for patients with advanced lung, ovarian, and thyroid cancer, the combination showed promise, and the findings will be reported at the American Society of Clinical Oncology (ASCO) annual meeting.
The drug combination was found to be effective against advanced malignancies with a variety of mutant variants of the KRAS gene, also known as the ‘death star’ because its protein has an impermeable, drug-resistant exterior and is the cause of one out of every four cancers, according to the trial.
Mutant variants of the KRAS gene are responsible for over 40% of lung cancers, 45% of bowel cancers, and 90% of pancreatic cancers, and KRAS mutations proved difficult to detect previously. The medications VS-6766 and everolimus were studied in a group of 30 patients with a variety of mutant KRAS gene variants, including 11 patients with advanced non-small cell lung cancer.
After six months, half of the lung cancer patients showed no signs of cancer progression, according to the findings. At this stage of the disease, the projected benefit of chemotherapy is nearly twice as long. Earlier trials that attempted to treat several KRAS variations in the same way failed due to severe side effects documented in patients, whilst the present experiment uses a new dosing strategy to reduce toxicity. The two medications were given twice weekly for three weeks in the phase one experiment, followed by a week off.
Patients in the experiment had previously received a variety of cancer therapies, including chemotherapy and cutting-edge immunotherapy, but their malignancies had halted reacting because their bodies had acclimated to the treatment and developed drug resistance. Two of the 11 patients with lung cancer who received the new drug combination therapy saw their tumours decrease by more than 30%, while the other nine patients saw their tumours grow slowly. People with high ovarian and thyroid malignancies responded to the combined therapy as well, and the researchers hope to extend this group of patients in the future.
Many groups have turned away from trying to simultaneously treat the two routes researchers know KRAS relies on to encourage growth since side effects were too extreme for patients, said deputy director of drug development at The ICR and The Royal Marsden NHS Foundation Trust, Professor Udai Banerji.
They are encouraged that by employing a unique dose regimen, they have been able to delay the progression of cancer in numerous patients who had exhausted all other therapy options. If similar results are seen in a larger number of individuals, this combination may be tested in larger clinical studies.
