The investigational personalised mRNA cancer vaccine mRNA-4157/V940 in combination with pembrolizumab (Keytruda) has been given a breakthrough therapy classification by the U.S. Food and Drug Administration (FDA) for the adjuvant treatment of patients with high-risk melanoma after complete resection.
The designation was made based on results from the phase 2b KEYNOTE-942 study.
The combination reduced the chance of recurrence or death by 44% compared to pembrolizumab alone, and the results showed that it met the trial's primary end point of recurrence-free survival. (RFS).
A single synthetic mRNA, designated as mRNA-4157/V940, can encode up to 34 neoantigens that were created and made using the distinct mutational profile of a particular patient's tumour. Neoantigen sequences from the immunization are endogenously translated and go through normal cellular antigen processing and presentation after injection.
In the open-label KEYNOTE-942 study, 157 stage III/IV melanoma patients were enrolled. Patients had to have a resectable cutaneous melanoma at high risk of recurrence, undergo a complete resection within 13 weeks of the first dose of pembrolizumab, be free of disease at study entry with no loco-regional relapse or distant metastases, and be devoid of any clinical signs of brain metastases.
Following resection, patients were randomized to receive either pembrolizumab alone or 9 total doses of mRNA-4157/V940 + 200 mg every three weeks for 18 cycles. Key secondary end points included distant metastasis-free survival and safety in addition to the main end point of RFS.
Regarding safety, adverse reactions (AEs) were consistent with data for pembrolizumab and mRNA-4157/V940 that had previously been described. In comparison to patients treated with pembrolizumab alone, 10% of patients who got mRNA-4157/V940 plus pembrolizumab experienced serious treatment-related adverse events (AEs).
