The Institute of Cancer Research and The Royal Marsden’s new drug combination shows promising results

The Institute of Cancer Research (ICR), London and The Royal Marsden NHS Foundation Trust have announced the results of phase 1 trial research evaluating a drug combination targeting multiple mutant versions of cancer’s ‘death star’ protein.

The combination has provided promise in an early-phase clinical trial for patients diagnosed with advanced lung, ovarian and thyroid cancer and the research will be presented at the American Society of Clinical Oncology (ASCO) annual meeting.

The trial showed that the drug combination was effective against advanced cancers that have a range of mutant versions of the KRAS gene, also known as the ‘death star’ because its protein has an impenetrable, drug-resistant surface and is the cause of one in four cancers.

Around 40% of lung cancers, 45% of bowel cancers and 90% of pancreatic cancers are fuelled by mutant versions of the KRAS gene and, until recently, KRAS mutations were very complex targets.

The trial tested the drugs VS-6766 and everolimus in a group of 30 patients with a range of range of mutant versions of the KRAS gene, including 11 patients with highly advanced, non-small cell lung cancer (NSCLC).

The results show that there has been no progression of the cancer for half of the group of patients with lung cancer after six months. This is about twice as long as the expected benefit of chemotherapy at such an advanced stage of disease.

Earlier studies aiming to treat multiple KRAS variants in a similar way were unsuccessful due to the severe side effects reported in patients, whereas the current trial employs an innovative dosing schedule to curb toxicity. Those involved in the phase 1 trial received the two drugs twice weekly for three weeks, followed by a week off.

Patients in the trial had already received several prior cancer treatments including chemotherapy and state-of-the-art immunotherapy, but their cancers stopped responding because their bodies had adapted to the treatment and had developed resistance to the drugs.

The new drug combination therapy caused tumours to shrink by over 30% in two of the 11 patients with lung cancer, while it controlled tumour growth in the other nine patients. Patients with advanced ovarian and thyroid cancers also responded to the combination therapy, and the researchers plan to expand this group of patients.

Professor Udai Banerji, deputy director of drug development at The ICR and The Royal Marsden NHS Foundation Trust, said: "Many groups have walked away from trying to simultaneously [treat] the two pathways we know KRAS relies upon to drive growth because side effects were too severe for patients.

"We are heartened that by using an innovative dosing schedule, we’ve managed to slow cancer’s progression in several patients who had run out of treatment options. If we see similar findings in a larger number of patients, we could see this combination taken through larger clinical trials."