Moderna and Merck’s personalised mRNA cancer drug has given cancer research an enormous boost in the treatment of melanoma. In a large Phase 3 trial, the mRNA formulation was found to by a lot lower the chances of the disease relapsing or metastasizing, when used together with an immunotherapy medication from Merck called Keytruda. The experimental drug intismeran autogene (with the code, V940, or mRNA-4157) is nothing like an ordinary vaccine that is available to everybody.
It is made in particular for every patient, based on the gene signatures of his/her tumor. Its purpose is to enable a patient’s immune system to target those cancer cells in his/her body which possess the mutant alleles specific to his/her genome.
The recent results are from the Phase 3 INTerpath-001 trial undertaken by intismeran, while 1,137 patients with stage IIB-IV melanoma that had been wholly excised were entered into the trail. The patients received either intismeran and Keytruda or Keytruda on its own.
The firms stated that the first outcome, an improvement in recurrence free survival met its primary objective, and also met a secondary secondary objective related to distant metastases. Both outcomes were described as significant and meaningful statistically by them.
The composition of the treatment depends upon the evaluation of a tumor from the patient. Researchers are able to determine mutations which may generate unique immune targets to the cancer (neoantigens).
This tailored treatment is capable of encoding for up to 34 neoantigens allowing other immune cells to recognize somatic features unique to the individual patient’s tumor. This is then used together with Keytruda an existing anti-PD-1 immunotherapy that assists the immune system in attacking the cancer.
This strategy aims to make an immune response that is more targeted than either therapy would be able to produce on its own. The most recent Phase 3 announcement is interesting, as the personalized mRNA cancer therapy has had one of the most impressive late-stage results so far.
Still, the full efficacy data (for numerical results for the clinical study) from the INTerpath-001 trial has not yet been announced by the companies, including the percentage reduction in recurrence risk. This data is due to be announced at a later date in a meeting.
Success of the Phase 3 trial rests on the promise of durable outcomes seen with previous Phase 2b KEYNOTE- 942 trial in high risk stage III and IV melanoma. At a median follow-up of roughly five years, intismeran plus Keytruda lowered the risk of recurrence or death by 49% compared with Keytruda alone.
It lowered the risk of distant metastasis or death by 59%. An exploratory analysis provided a promising trend in overall survival, although the trial was not powered to demonstrate overall-survival.
Melanoma can be classified as a most dangerous cancer of the skin as it has a tendency to recur after surgical removal and metastasize to other body sites. Even with complete removal of the tumor there is the potential for some microscopic cancer cells to remain undetected.
This strategy by the Moderna-Merck is attempting to address this issue by utilizing a patient’s accumulated tumor mutations to assist in championing the immune system to the possible existing cancer cells.
