A new phase I/IIa trial known as the MAGE vaccine trial is expected to enrol approximately 86 people who have been newly diagnosed with non-small cell lung cancer (NSCLC). The trial follows promising preclinical research in mouse models by Professor Benoit Van den Eynde’s group at Ludwig Oxford and will be testing the safety and initial efficacy of the VTP-600 cancer vaccine in these patients. VTP-600 will be given in combination with the current first line treatment for NSCLC.
Unlike preventative vaccines, such as the influenza vaccine, which is given to healthy people to protect them against future disease, VTP-600 is given to people who already have lung cancer. VTP-600 is an immunotherapy, designed to stimulate the body’s immune system to attack cancer cells.
It does this by delivering cancer-associated proteins — known as MAGE-A3 and NY-ESO-1 antigens — to antigen presenting cells (dendritic cells), causing the immune system to produce cytotoxic T cells which are able to target and kill cancer cells expressing these antigens. It cannot target healthy tissues because MAGE-A3 and NY-ESO-1 are not found on non-cancerous cells.
VTP-600 is a ‘prime-boost’ immunotherapy, meaning an initial ‘prime’ dose is administered, and then a second ‘booster’ dose is given 21 days later. This ‘prime-boost’ approach is expected to improve the size and length of the anti-cancer immune response.
Even though two doses are administered, the immunotherapy comprises three parts. ChAdOx1-MAGE-A3-NY-ESO-1 is the prime immunotherapy administered to all patients and then MVA MAGE-A3 with or without MVA NY-ESO-1 is given as the second booster immunotherapy, depending on the type of antigens expressed on the patient's tumour.
In the prime dose, ‘ChAdOx1’ refers to the viral vector used in the vaccine to deliver the antigens. It is a virus which causes a common cold in chimpanzees, but it has been modified so that it can no longer cause disease. ChAdOx1 is the same viral vector used in the Oxford/AstraZeneca Covid-19 vaccine and is being used in phase II trials for other diseases.
In the boost doses, ‘MVA’ is a second viral vector containing the MAGE-A3 or NY-ESO-1 antigens, and is a Modified Vaccinia Ankara virus, which is a type of poxvirus which has been severely weakened so that it can no longer cause disease.
If further clinical trials are successful, VTP-600 could prove to be a powerful new treatment for a group of patients in need of better options. Depending on its effectiveness in NSCLC, VTP-600 could be evaluated in other types of cancer in the future, including breast, bowel, bladder and melanoma.
We are pleased that the research arising from the Ludwig Oxford Branch and their colleagues at Oxford University is being tested in this clinical trial to evaluate the benefit it may bring to patients with NSCLC and potentially other cancer patients as well. - Jonathan Skipper, Executive Vice President for Technology Development, Ludwig Institute for Cancer Research.
The trial is expected to run over 2-3 years. More information on the clinical trial can be found at NCT04908111. Cancer Research UK’s Centre for Drug Development (CDD) is managing and providing significant funding for the phase I/IIa trial. Vaccitech Oncology Limited (VOLT), a strategic collaboration between Vaccitech and Ludwig, are supplying VTP-600 for the trial.
There is an urgent need to find better treatments for patients with NSCLC. The VTP-600 immunotherapeutic vaccine is a cutting-edge technology to target a patient’s immune system to tackle the cancer cells. The trial is planned to open at 10 specialist hospitals across the UK to ensure that as many patients as possible can be given opportunity to participate. - Chief investigator for the MAGE clinical trial, Professor Fiona Blackhall, who is consultant medical oncologist and director of research and innovation at The Christie NHS Foundation Trust
We are excited to see that the first patient has been treated with the VTP-600 immunotherapeutic vaccine. NSCLC is the most common type of lung cancer but remains very hard to treat. If successful, this cutting-edge immunotherapy could provide an effective, much-needed new treatment to help more people survive their lung cancer. Partnering with Vaccitech and the Ludwig Institute was vital for making this trial a reality, and we are looking forward to seeing how the trial progresses. - Dr Nigel Blackburn, Director of Cancer Research UK’s Centre for Drug Development