Cancer Research UK and its commercial arm Cancer Research Technology (CRT) are launching a trial of an experimental drug shown to simultaneously block many enzymes that control cancer cell growth and death.

The ‘master-switch’ experimental drug, owned by Astex Pharmaceuticals, could potentially treat a range of cancer types.

Cancer Research UK’s Drug Development Office (DDO) will fund, manage and sponsor this early-stage Phase I clinical trial of up to 40 patients at The Institute of Cancer Research, London, and The Royal Marsden Hospital.

The drug, AT13148, is one of eight drugs to be developed through Cancer Research UK’s Clinical Development Partnerships (CDP) programme, which is a joint initiative between the charity’s DDO and CRT.

The programme develops promising cancer drugs that pharmaceutical companies do not have the resources to progress through early phase clinical trials to see if they can benefit cancer patients. Without this programme many promising drugs would be left on the shelves gathering dust.

AT13148 is a type of drug called a kinase inhibitor. Research in the laboratory has shown it can simultaneously block several different enzymes that control cell growth and cell death, and the drug killed a range of cancer cell types including sarcoma, breast and prostate. Many drugs block only a single enzyme and scientists hope that switching off cell signals at multiple points at the same time could increase the effectiveness of this drug.

Dr Udai Banerji, Cancer Research UK senior clinical lecturer at The Institute of Cancer Research and honorary consultant in medical oncology at The Royal Marsden, said: “There’s an urgent need to discover and develop new ways to beat cancers that do not respond to the treatments we have at the moment. By targeting cancer cells at a range of weak spots instead of just one, tumours will be less likely to develop resistance to this treatment. We’re very pleased that this multi-target drug has now reached patients in the clinical trial stage.

“It’s thanks to the generosity and time of patients that it’s possible to carry out clinical trials like this that could lead to new treatments for patients in the future.”

The novel agent came into the DDO requiring extensive preclinical development work.

Cancer Research UK scientists at the DDO and those funded at The Institute of Cancer Research demonstrated that the drug would be suitable for patients and, working together with specialist manufacturing organisations, developed a sophisticated method to make the drug in its most basic form. Finally, Cancer Research UK’s Formulation Unit at the University of Strathclyde manufactured the drug for the trial.

The molecule was originally discovered by scientists on the PKB drug discovery programme, a collaboration between Astex Pharmaceuticals, CRT and The Institute of Cancer Research, which ran from 2003 through to 2006.

Harren Jhoti, Astex Pharmaceuticals president and director, said: “We are very gratified with the progress that the collaboration has achieved and that this work has progressed into the clinic.”

Astex Pharmaceuticals can decide to develop the drug further based on the Phase I/IIa clinical trial data. If it chooses not to, Cancer Research Technology has the rights to secure an alternative partner and ensure the drug has every possible chance of reaching patients. The charity will receive a share of revenues generated by the drug to be channelled back into life-saving research.

Dr Victoria John, head of clinical partnerships at Cancer Research UK’s Drug Development Office, said: “We’re delighted to open the first clinical trial of this experimental drug to find out if it can benefit cancer patients in the future.

“This molecule was brought to us at a very early stage in its development and, with the preclinical work now completed, we’re extremely pleased it’s obtained regulatory approval to enter the clinic.

“We’ve developed this molecule through our Clinical Development Partnerships initiative that has allowed us to form strong links with industry to take this promising drug forward. Without the programme it may have remained undeveloped and the clinical trial simply would not have been possible.”

Source: CRUK