Merck and Moderna say melanoma mRNA vaccine delayed recurrence in interim trial results
Merck and Moderna reported positive Phase 3 results for a personalized melanoma treatment, but detailed data and regulatory review are still pending.
By Tom Brennan · Health & Medicine Correspondent
3 min read
Merck and Moderna say their melanoma mRNA vaccine, used with the immunotherapy Keytruda after surgery, met key goals in a Phase 3 trial for people at high risk of the cancer returning. The announcement could mark progress for a narrowly defined group of melanoma patients, but the companies have not released the detailed interim data or published them in a peer-reviewed journal.
The treatment, intismeran autogene, is an investigational individualized mRNA neoantigen therapy also known as V940 or mRNA-4157. It is being tested alongside pembrolizumab, sold as Keytruda, an anti-PD-1 immunotherapy made by Merck.
What did the melanoma mRNA vaccine trial find?
Merck and Moderna reported Aug. 19 that the Phase 3 INTerpath-001 study met its main measure, recurrence-free survival, and a key secondary measure, distant metastasis-free survival, at a planned interim analysis. The companies described the improvements over Keytruda alone as statistically significant and clinically meaningful, according to BioPharm International.
The study enrolled 1,137 people whose stage IIB through IV melanoma had been completely removed by surgery and who had not previously received systemic treatment, BioPharm International reported. Participants were assigned two-to-one to receive the combination or Keytruda alone for about a year.
Those results have not yet been presented in full. NBC News reported that the companies planned to take the data to a medical meeting and share it with regulators, while the trial continues to assess overall survival. No regulatory filing had been submitted when the results were announced, according to BioPharm International.
What is this treatment designed to do?
This is not a routine shot intended to prevent skin cancer in healthy people. It is a post-surgery treatment for people with resected cutaneous melanoma, designed to reduce the chance that cancer returns or spreads.
For each patient, a tumor sample is sequenced to identify mutations unique to that tumor. Intismeran is then made to encode up to 34 of those tumor-specific neoantigens, with the aim of prompting a T-cell response directed at the cancer, BioPharm International reported. That individualized process distinguishes it from standard preventive vaccines, which use the same formulation across broad groups of people.
Is the melanoma mRNA vaccine available yet?
No. Intismeran remains investigational, and the new Phase 3 announcement does not establish when, or whether, it will receive regulatory authorization. Readers should also separate the company-reported interim Phase 3 finding from the earlier evidence that has been presented and published.
In the earlier randomized Phase 2b KEYNOTE-942 study, Merck and Moderna reported at a median 60.3 months of follow-up that the combination cut the risk of recurrence or death by 49% compared with Keytruda alone. It also reduced the risk of distant metastasis or death by 59%, according to the companies' June update; NPR reported the five-year findings were published in the Journal of Clinical Oncology.
The Phase 2b overall-survival analysis was exploratory, with a wide confidence interval, so it did not demonstrate a survival benefit. In that study, the most common treatment-attributed side effects were fatigue, injection-site pain and chills; Merck and Moderna said most were mild or moderate and reported no attributed grade 4 or 5 events.
This story draws on original reporting from NBC News.