Consultant Medical Oncologist Dr James Larkin led a trial that treated melanoma with immunotherapy

Consultant Medical Oncologist Dr James Larkin led a trial that treated melanoma with immunotherapy

Immuno-oncology is an area of research that explores interaction between cancer and the immune system in order to find new treatments, using the body’s own immune system against tumours.

The Royal Marsden has been involved in the clinical trials of many of the drugs used in these treatments, working with the major pharmaceutical companies. In addition, it is one of the Centres of Excellence in the Roche imCORE Network, which spans nine countries and brings together 21 of the world’s leading academic, scientific and clinical experts in cancer immunotherapy to collaborate in investigating the most promising new approaches in treatment.

Professor David Cunningham, Director of Clinical Research at The Royal Marsden, says:

“Immunotherapy has been a game-changer in the treatment of cancer, and The Royal Marsden has been at the forefront of these developments. It has provided us with an option for cancers that are normally resistant to standard drugs, such as metastatic melanoma and kidney cancers.

“Historically, immunotherapy has been well tolerated but inactive, and hasn’t benefited many patients. This has changed dramatically in recent years. The new agents benefit many patients but have a spectrum of toxicity that needs to be managed carefully.”

Successes so far

Pembrolizumab and nivolumab are two monoclonal antibodies used against melanoma, non- small-cell lung cancer, kidney cancer, bladder cancer, head and neck cancers, and Hodgkin lymphoma. Both have been trialled at The Royal Marsden. Nivolumab in combination with ipilimumab has also been successful in treating melanoma.

A trial led by Dr James Larkin, a Consultant Medical Oncologist specialising in melanoma at The Royal Marsden, showed that in 58% of patients, the two drugs combined shrank tumours and stopped the cancer advancing for nearly a year on average.

Dr Larkin says: “By giving these drugs together, you are effectively taking two brakes off the immune system rather than one. The immune system is able to recognise tumours it wasn’t previously recognising and destroy them.”

In another groundbreaking trial, a genetically engineered herpes simplex virus was shown to halt the progression of melanoma. T-VEC is a modified form of the virus that multiplies inside cancer cells and bursts them from within, and stimulates the immune system to destroy the tumour.

Responses to treatment were most pronounced in patients with less advanced cancers and those who had yet to receive any treatment – showing the potential benefits of T-VEC as a first-line treatment for metastatic melanoma that cannot be removed surgically.

UK trial leader Professor Kevin Harrington, Consultant Clinical Oncologist at The Royal Marsden, says: “There is increasing excitement over the use of viral treatments because of their two- pronged attack – both killing cancer cells directly and marshalling the immune system against them.”

We are now enhancing our research in several areas.

New cancer types

Following the success of the combination of ipilimumab and nivolumab in melanoma, we’re looking at extending its use into head and neck, bladder, lung and kidney cancers and Hodgkin lymphoma.

Nivolumab has already been approved to treat kidney cancer, and Dr Larkin is looking at other immunotherapy combinations for this disease. In lung cancer, Consultant Medical Oncologist Dr Sanjay Popat is leading the PROMISE-MESO trial for patients with advanced mesothelioma. We’re looking to develop immunotherapy for breast and gynaecological cancers, and are running immunotherapy clinical trials for children and young people.

Treatment combinations

We’re combining immunotherapy with other forms of treatment such as radiotherapy, vaccines and chemotherapy. Radiotherapy has the potential to activate anti-tumour immune responses, and this may be enhanced further in combination regimens with immunotherapy. We’re trialling pembrolizumab in combination with radiotherapy in four different tumour types: bladder, cervical, head and neck, and lung.

Adjuvant treatments

We are looking into using ipilimumab as an adjuvant treatment – a medicine given to patients as a precaution to prevent the cancer returning. The aim is to establish if we can administer treatment earlier to prevent the relapse of melanoma and kidney cancer following surgery.

Dr Mary O’Brien, Consultant Medical Oncologist, is leading the PEARLS trial, which is studying pembrolizumab in patients who have had curative surgery for lung cancer.

She says: “The adjuvant clinical trials are potential game-changers. The Royal Marsden is leading the way, giving patients the best treatment options from the moment they step through the door.”