New cancer drug shows signs of promise in early-stage trial

Date:
14 October 2014

An investigational drug which can block the activity of a common mutation in cancer has shown promise in its first patient trial, a new study reports.

A team from The Institute of Cancer Research, The Royal Marsden and other UK collaborators tested the drug, called CH5132799, on patients with various types of advanced cancer.

They found that the drug was well tolerated by the patients and that it showed evidence of inhibiting the PI3 Kinase (PI3K) pathway, which is mutated and often hijacked in a range of cancers, including breast, ovarian and lung.

The results, published online in the journal Clinical Cancer Research, were funded by Chugai Pharmaceutical Co., Ltd., with additional support from Cancer Research UK, the Experimental Cancer Medicine Centre and the NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research (ICR).

The PI3K signalling pathway is important for many cellular processes linked to the growth and spread of cancer, and also for resistance developing to treatments. Drugs that work by blocking the PI3K pathway could potentially treat a wide range of human cancers.

Previous research in the lab has shown that CH5132799 can treat cancer cells which have PI3K mutations, and this clinical study suggests the drug could also be effective in patients, to be tested further in larger clinical trials.

Researchers gave CH5132799 to 38 patients with solid tumours and monitored their response. They found that the drug did not cause serious adverse effects to patients at the recommended dose for clinical use and that there was also evidence of anti-tumour activity.

Sophisticated bespoke phosphoprotein blood tests were conducted in the Pharmacodynamics lab at the ICR. Patient blood samples indicated significant inhibition of PI3K signalling, and in 23 patients who were scanned to measure changes in tumour metabolism, as a marker for CH5132799 activity, they found that CH5132799 inhibited tumour metabolism in 17 patients.

They also found that two patients with ovarian and breast cancer saw a clinical benefit from the early-stage drug, improving or maintaining their disease symptoms for nearly six months.

Dr Udai Banerji, Cancer Research UK Senior Lecturer at The Institute of Cancer Research and Honorary Consultant at The Royal Marsden NHS Foundation Trust, said: “There are many tumours with abnormalities in the PI3 kinase signalling pathway, so drugs targeting it could potentially treat a wide range of cancers. This is an early-stage clinical trial but our study shows that CH5132799, which was developed by Chugai Pharmaceuticals and can block a range of PI3 Kinases, achieved all the endpoints we were evaluating. Our trial shows that CH5132799 is well tolerated to use in patients and that it can inhibit the PI3K pathway, with early evidence that it could be effective in patients.

“The ICR has a strong track record of discovering and developing PI3K inhibiting drugs and our work with biological markers to verify CH5132799’s activity was crucial for determining the right dose schedule. This drug is another exciting molecule targeting the PI3K pathway, which has now completed phase I trials."