A major breakthrough in research into cancer vaccine development has been announced in the U.S., with the first positive Phase 3 clinical results for personalized mRNA therapy.
However, an important clarification is needed: intismeran, which is not yet an approved vaccine against melanoma to be precise, is a treatment under investigation, and the results announced yesterday are the first positive results of the Phase 3 clinical for personalized cancer treatment based on next-generation, mRNA technology.
What exactly he achieved
Intismeran autogene (V940, formerly mRNA-4157) is developed by Moderna in collaboration with Merck (MSD outside the US) and is administered in combination with Keytruda (pembrolizumab).
The Phase 3 INTerpath-001 study enrolled patients with fully operated stage IIB–IV melanoma. The study compared:
- Keytruda + personalized intismeran
- Keytruda alone
It achieved both the primary endpoint, i.e. improvement in recurrence-free survival (RFS), and the key secondary endpoint, distant metastasis-free survival (DMFS).
Simply put: patients who received the combination had a significantly lower risk of recurrence of melanoma and a lower risk of metastasizing to other organs, compared to Keytruda alone.
How the "personalized vaccine" works
After the tumour is removed, the genetic profile of the specific tumour is analyzed to identify mutations that create the so-called neoantigens. Based on these mutations, a personalized mRNA is designed for the specific patient. mRNA instructs the immune system to recognize and attack cancer cells that carry these characteristics.
Keytruda works differently: it blocks the PD-1 pathway and essentially "releases the brakes" of the immune system. Thus, the two treatments have a complementary role.
When can it be made available?
Moderna and Merck have said they intend to submit for approval to regulators in the coming months. But this does not mean that the vaccine will be available to patients in the coming months. It should first be evaluated and approved by FDA, EMA, and other relevant authorities.
Why is it considered a historic result
What is particularly important is not just that it is a new technology, mRNA. It is that this is, according to the companies and the reports so far, the first personalized mRNA-based neoantigen therapy that gave a positive result in a Phase 3 study.
In fact, there is already previous evidence that the effect is not accidental: in the Phase 2b KEYNOTE-942 study, with a five-year follow-up, the combination had shown a 49% reduction in the risk of recurrence or death compared to Keytruda alone.
