Cross-company collaboration to trial combination of immunotherapy drugs in fight against mesothelioma

Posted: 17th Nov 16 10:53 AM

Cancer Research UK has announced its first cross-company deal as part of its Experimental Cancer Medicine Centre (ECMC) Combinations Alliance.

MSD, Verastem Inc. and Cancer Research UK will trial a new combination of immunotherapy drugs in mesothelioma, non small cell lung cancers and pancreatic cancers. The trial is planned to be run through the ECMC network centres across the UK.

The trial will investigate whether a focal adhesion kinase (FAK) inhibitor drug from Verastem called VS-6063 (Defactinib) can boost the effectiveness of a PD-1 immunotherapy drug from MSD called Keytruda.

It is based on discoveries made by scientists at the Edinburgh Cancer Research UK Centre at the University of Edinburgh, who showed that inhibiting FAKs can reduce the cancer immune response. Defactinib may be able to take down a barrier of immune cells which are tricked into protecting the cancer cells, while Keytruda can activate cancer-killing immune cells to attack the exposed cancer cells.

The trial will consist of around 50-60 cancer patients, who will take the drug combination, starting with small doses and building up to find what is safe. The scientists will also study how the treatments target cancers and what effects the drug combination has on the tumours.

Dr Mercia Page, medical director of oncology at MSD, said: “We look forward to working with Cancer Research UK and Verastem on this promising combination. Strategic collaborations such as this reinforce the commitment we have to bringing a range of new treatments to the forefront, helping people with cancer who need a number of options available to them.”

Dr Greg Berk, Verastem’s chief medical officer, said: “Combining defactinib and MSD’s [Keytruda] through the Combinations Alliance expands our potential to deliver transformative therapies to patients with many types of cancer.

“We are delighted to be working with the Combinations Alliance, MSD and world class scientists and medical centres throughout the UK on this trial. This study will build on the single agent activity of defactinib observed in early clinical trials in patients with non-small cell lung cancer and other tumour types, and follow from substantial preclinical research which has demonstrated that FAK inhibition optimises the tumour immune balance.”

Dr Ian Walker, director of clinical research at Cancer Research UK, said: “It’s vital that we find new treatments for these three cancers which take tens of thousands of lives each year in the UK and we’re delighted to be working with MSD and Verastem on this.

“Our Combinations Alliance was set up to help develop partnerships between drug development companies and researchers to try new combinations of drugs in the hope of improving treatments and saving more lives from cancer. This is our first success in bringing together two organisations and we hope that this combination of immunotherapy drugs will benefit patients.”

Mesothelioma, pancreatic and non-small cell lung cancers all have very low survival – with more than half (60%) of mesothelioma patients, more than three quarters (79%) of pancreatic cancer patients and two thirds (68%) of lung cancer patients dying within a year if diagnosis in England and Wales.”

Trial co-lead Dr Stefan Symeonides, from the University of Edinburgh, said: “Immunotherapy is a very exciting area of cancer research and we’ve seen remarkable benefits from [Keytruda] for some patients with hard-to-treat cancers, like melanoma and lung cancer. We’re hoping that the addition of Defactinib will extend those benefits to more patients.

“This work could one day give a new treatment option that saves lives for this group of patients who have few options.”

What is mesothelioma?

Mesothelioma is an incurable cancer caused, in the vast majority of cases, by exposure to asbestos dust and fibres.

It is quite a rare cancer, but it is becoming increasingly more common. Figures from the Health and Safety Executive show that more than 2,500 people are diagnosed with pleural mesothelioma in the UK each year and according to the Department for Health and Pensions, 53,000 people will die from pleural mesothelioma between 2013 and 2037.

It is estimated that in the UK, more than 9 out of 10 men with mesothelioma and more than 8 out of 10 women have been in contact or were exposed to asbestos dust and fibres. We know that exposure to asbestos is the leading cause of pleural mesothelioma.

Asbestos is a fibrous material that was widely used for its fire resistant and insulating properties until the late 1990s. The use of asbestos is now banned in the UK and there are strict guidelines about its safe removal.

Dr Robin Rudd, a medical expert in mesothelioma and asbestos cases, has stated: “Mesothelioma can occur after a low level of asbestos exposure and there is no threshold dose of asbestos below which there is no risk.”

This means that inhaling even a single asbestos fibre could potentially cause mesothelioma.

Pleural mesothelioma is typically fatal within one year of diagnosis, but research into potential treatments is slowly improving.