In the aftermath of the presentation of the first randomized study of an mRNA vaccine against melanoma at the American Association for Cancer Research meeting, and a week after Moderna’s chief medical officer told the Guardian, in which the company revealed that aiming to bring these vaccines against different types of cancer into the clinic in just 5-7 years, the attention of the scientific (and non-scientific) world towards this strategy is decidedly high. “We finally have the data, and I can say with pride and not a little emotion that we are at the beginning of a new possible revolution: a personalized vaccine that helps the immunotherapy currently in use, and which could become a pan-tumor strategy, not only for melanoma,” he says Paolo Ascierto, director of the Melanoma Oncology, Oncological Immunotherapy and Innovative Therapies Unit of the ‘Pascale’ Institute of Naples and president of the Melanoma Foundation. His research group will participate in the multicenter phase 3 study on the combination of the Moderna vaccine and immunotherapy with pembrolizumab, the one that will decree the effective effectiveness of this strategy and which could start at Pascale as early as June with the first enrollments.
Melanoma, the first data on the combination of the mRNA vaccine and immunotherapy are positive
by Tiziana Moriconi
Evaxion’s mRNA vaccine
Meanwhile Ascierto, together with other research groups, is participating in another clinical trial on another mRNA vaccine, always in combination with immunotherapy and always in patients with melanoma. However, unlike the patients involved in the Moderna study, they have active metastatic disease (that is, the metastatic tumor is present and not resected): the vaccine and immunotherapy are therefore administered as the first line of treatment, and not as adjuvant treatment ( to prevent recurrence). “It is a non-randomized and open-arm phase 2 study, which has recently also involved Italian centers and is funded by the biotech Evaxion – he tells Oncoline the expert – Conceptually it is very similar to the study just presented: it is based on an mRna vaccine administered in combination with an anti-PD-1 immunotherapy. Again, a piece of tumor tissue is processed to make the mRNA vaccine; in the meantime the patient starts treatment with pembrolizumab and, after about 8 weeks, this vaccine is added”.
Moderna’s vaccine data that gives hope
As a rule, explains Ascierto, the drugs are first tested in the metastatic phase and then tested even in the earliest stages of the disease. With the study by Moderna and MSD (Keynote 942) the opposite path was taken: “If it is true that the results of the phase 2 studies must always be taken with a grain of salt, the absolute benefit observed at 18 months of 18.4% is really important – underlines Ascierto – The recurrence-free survival was in fact 78.6% in the combination group against 62.2% in the monotherapy group with pembrolizumab. These data are even more interesting if we consider that up to now the combination of two immunotherapies has always failed, because it has never been shown to be more effective than monotherapy. Additionally, the toxicity profile was similar between the two groups. All this gives us hope in the possibility of identifying a new combination strategy also for metastatic patients”.
Vaccines against cancer and heart attack: the mRNA revolution
by Tiziana Moriconi
Up to 34 “target” proteins
These mRna vaccines are personalized, as has been mentioned several times. It means that we start from the patient’s tumor and analyze it in search of its targets, i.e. the neoantigens (molecules recognized as foreign by the body): an algorithm selects those that have the greatest probability of triggering the immune response and developed the vaccine. “In the study just presented, in 90% of cases the tumor tissue was sufficient to conduct the analysis – continues Ascierto – Of these patients, 91% received a vaccine directed against 34 different antigens. Of the remaining 9%, the neoantigens useful for constructing the vaccine varied in number: from a minimum of 9 to a maximum of 32″.
Research: one euro invested in a clinical study generates almost three
by Irma D’Aria
In short, everything points to a good starting point: “It is an innovative strategy that allows for the personalization of the treatment and, conceptually, it is applicable to all other types of tumors, starting from those in which immunotherapy has already given good outcomes, such as lung and kidney cancer. I believe – he concludes – that we are on the road that will lead us to improve immunotherapy”.