First patient receives new ‘resistance-busting’ panRAF inhibitor in skin cancer drug trial

A patient has become the first to receive a new ‘resistance-busting’ experimental skin cancer drug with the launch of a phase I clinical trial.

The patient has received a new panRAF inhibitor – a new type of drug under development to address the problem of drug resistance in advanced skin cancer and a number of other cancer types. PanRAF inhibitors block several key cancer-causing proteins at once including BRAF, which drives about half of all melanomas. Existing BRAF inhibitors are designed to block that protein – but most patients develop resistance to them within a year.

The trial is the culmination of a pioneering research programme to design, synthesise and develop the new drug class, led by scientists at The Institute of Cancer Research, London, and the Cancer Research UK Manchester Institute at The University of Manchester. It is starting just three months after a major publication in the journal Cancer Cell described the potential of this new drug class, which is potentially able to treat melanomas – the most serious type of skin cancer – that do not respond or have become resistant to existing therapies.

Phase I trial will recruit around 25 patients with advanced, solid tumours

The phase I trial of the drug – which is yet to be given a formal name and is currently known as BAL3833/CCT3833 – is sponsored by The Institute of Cancer Research (ICR) and The Royal Marsden NHS Foundation Trust. The trial is funded by the Wellcome Trust, the NIHR Biomedical Research Centre at The Royal Marsden and the ICR, The Christie charity and the Cancer Research UK Manchester Institute.

The trial will recruit around 25 patients with advanced, solid tumours – focusing on advanced melanoma – with the aim of establishing the safe maximum dose for a planned phase II clinical trial.

Just last month, a new consortium was announced to develop this drug class for patients – following an agreement between academic organisations, funders and Swiss-based biopharmaceutical company Basilea Pharmaceutica International Ltd. This consortium – including the ICR, the Wellcome Trust, Cancer Research Technology (CRT) and the Cancer Research UK Manchester Institute/The University of Manchester – has granted Basilea exclusive worldwide rights to develop, manufacture and commercialise a series of novel panRAF inhibitors.

Basilea will assume full operational responsibility for the research programme after the phase I trial, and is also carrying out biomarker research along with the Cancer Research UK Manchester Institute.

Trial on new panRAF inhibitor comes just three months after publication of laboratory results

Professor Caroline Springer, Professor of Biological Chemistry at The Institute of Cancer Research, London, and leader of the ICR’s panRAF inhibitor research programme, said, “Our new inhibitors are an example of an exciting new approach to cancer treatment that knocks out several important cancer signals at once, in order to treat cancers that develop resistance to drugs targeted at just one cancer signal.

“It’s very exciting to go from publication of our laboratory results on panRAF inhibitors to assessment of the new treatment in the first patient in just three months. It demonstrates our belief in the promise of this work, and our desire to attempt to deliver benefits for patients as quickly as possible.”

Dr James Larkin, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, who is leading the clinical trial, said, “The major problem with current targeted therapies is resistance to treatment. This drug has been developed in the laboratory specifically to tackle this problem and we are very excited to be treating the first patient in this clinical trial.”

Professor Richard Marais, Director of the Cancer Research UK Manchester Institute and leader of its panRAF inhibitor research programme, said, “BRAF drugs can give valuable extra months of quality life to about half of melanoma patients, but sadly it is not a cure and most patients eventually develop resistance. These new drugs are engineered to get around this problem by shutting down the routes that tumours use to bypass BRAF drugs. They work very well in the laboratory and we look forward to now seeing if they also work well in patients.”

Dr Paul Lorigan, Reader in Medical Oncology at The Christie NHS Foundation Trust, said, “We are very excited that this new treatment, borne out of great innovation and collaboration, will potentially make a real difference for our patients with melanoma.”