Personalised treatment trialled for aggressive asbestos-linked cancer

A new trial is investigating a personalised treatment for patients with a rare and aggressive form of cancer.

Mesothelioma is a cancer that forms in the lining of the lungs or abdomen. It is linked to exposure to dangerous asbestos fibres.

Around 2,700 people are diagnosed with the disease each year. Outcomes and survival rates are poor.

The SELECTmeso1 trial is investigating whether a targeted cancer treatment can improve outcomes for patients who have a particular genetic biomarker.

It is due to open at 10 hospitals across the UK, including at University Hospital Southampton.

The trial is led by Professor Dean Fennell from the NIHR Leicester Biomedical Research Centre (BRC) and Professor Gareth Griffiths from the NIHR Southampton BRC.

It is run by the Cancer Research UK Southampton Clinical Trials Unit (SCTU), with funding from Asthma + Lung UK. The trial is sponsored by the University of Southampton.

Targeting a ‘weak point’

There are currently very few treatment options for people with mesothelioma. The cancer often returns after initial treatment. Only around five per cent of people diagnosed with the disease will survive for five years or more.

Recent trials by the NIHR Leicester BRC and SCTU have shown targeted treatments can improve survival for people with relapsed mesothelioma, where the disease has come back.

However, these treatments often only work for some patients, but not for others.

Professor Fennell is Chief Investigator of SELECTmeso1. He is Chair of Thoracic Medical Oncology at the University of Leicester.

“This is due to the genetic make-up of people’s individual cancer and the specific biomarkers, or genetic signals, their cancer has,” he said.

“But imagine if there was a way to tell which treatment is likely to work best for each patient and personalise the care they get, giving them best chance of a successful outcome.

“The SELECTmeso1 trial is doing just that. We know that almost half of patients with mesothelioma have a deletion of a particular gene called MTAP. This means they have a more aggressive cancer, and don't respond as well to existing treatments.

“However, the absence of this gene creates a unique weak point in their cancer cells that healthy cells don't have, meaning the cancer cells are able to grow uncontrolled. This is the genetic pathway we are targeting in this trial.”

The team are working with pharmaceutical company Bristol Myers Squibb, who have developed a treatment called Navlimetostat.

This medicine targets the weak point created by the absence of the MTAP gene. The drug selectively kills those cancer cells, leaving the healthy cells largely unaffected.

Promising anti-tumour properties

Professor Gareth Griffiths is co-Chief Investigator of SELECTmeso1. He is Director of the SCTU.

“This drug has already been trialled in some other cancers and has been shown to have promising anti-tumour activity,” he said. “It was also well tolerated by patients without causing too many side effects.

“Through the SELECTmeso1 trial, we therefore hope to find out whether this could be a viable treatment for patients with this specific genetic signal. If we find evidence that patients benefit, this will hopefully lead to future practice-changing trials.”

Patients with relapsed mesothelioma who are found to have the deleted MTAP gene will be invited to join the SELECTmeso1 trial.

They will be given the targeted treatment in the form of tablets every day, in three-weekly cycles, for up to six months.

The research team will monitor how much their tumour shrinks. They will also record any side effects they experience.

Progress ‘desperately needed’

The trial recently opened at Leicester Royal Infirmary, where the first patients have been recruited.

Dr Samantha Walker is Director of Research and Innovation at Asthma + Lung UK.

“Asthma + Lung UK is proud to be funding this vital research, which could be a real breakthrough and has the potential to improve the lives of people living with mesothelioma,” she said.

“With life expectancy remaining low and no current cure available, progress on treating this devastating condition is desperately needed.

“Targeted therapy has already shown to be effective for other types of cancer. If this trial is successful, it would offer new hope for the more than 2,000 people who are diagnosed with mesothelioma every year.

“Cutting edge research into new types of treatment for lung conditions is vital to improve health outcomes. However, funding for lung health research is currently on life-support, despite lung conditions remaining the third biggest cause of death in the UK.”

It is the first trial supported by the newly formed UK collaborative for clinical cancer research's (UK3CR’s) Mesothelioma Clinical Research Group, chaired by Professor Fennell. This has the remit to develop trials for mesothelioma patients in the UK.

Looking for more targets

SELECTmeso1 is the first trial in a much larger planned platform clinical trial. This aims to test several drugs that target genetic biomarkers that may be present in a patient’s tumours.

Dr Emma Knox is Senior Trial Manager for SELECTmeso at the SCTU.

“The idea of the platform trial is that we can run several different trials at once, giving patients more chance of receiving a treatment that works for them,” she said.

“Once the full platform is open, patients will be invited to join, and will have a sample of their cancer tested in a laboratory. This will tell doctors about the particular genetic make-up of their cancer and what biomarkers their mesothelioma has.

“If there is a trial within the platform that is testing a drug that works specifically for that biomarker, they will be invited to join that particular trial.”

If there is no trial running for that biomarker at that time, patients will remain in the platform database. They will be contacted if a new trial of a treatment that may work for them starts.

Each separate trial within the SELECTmeso platform will recruit 26-30 patients. The trials will take place at hospitals around the UK.

“The aim of the platform is to test how effective each drug is for patients with those specific biomarkers, and to see whether stratifying treatment in this way can improve outcomes for patients,” said Professor Fennell.

“The hope is that in the future, doctors treating people with this aggressive cancer will be able to use a more personalised approach, selecting the best possible treatment for each individual patient.”