A new individualized mRNA-based melanoma vaccine is now in Phase 3 trials in the UK.
The Phase 3 clinical trial, led by researchers at the University College London Hospitals NHS Foundation Trust (UCLH), is evaluating the combination of mRNA-4157 (V940) and pembrolizumab (Keytruda, Merck) versus a current standard of care (pembrolizumab) as a risk-reducing treatment option for patients with resected, high-risk, stage IIB to IV melanoma.
The trial, named INTerpath-001, will enroll around 1,089 patients across the world. The primary outcome measure is recurrence-free survival, with overall survival and metastasis-free survival as secondary outcomes.
To create the vaccine, a tumor sample is removed and DNA is sequenced – with artificial intelligence also playing a role. The personalized treatment instructs the body to make up to 34 proteins, each targeting ‘neoantigens’ identified by gene sequencing and thought to be driving the cancer in that particular patient. The neoantigens are proteins found only on the cancer cells, and the individualized neoantigen therapy is designed to prime the immune system to attack the tumor cells in each patient, while pembrolizumab blocks an immunological ‘brake’ that protects cancer.
The technology was developed by Moderna in conjunction with Merck Sharp and Dohme (MSD).
“The idea behind this immunotherapy is that, by prompting the body to make these proteins, it can prepare the immune system to quickly identify and attack any cancer cells bearing them, to prevent recurrence of melanoma,” says medical oncologist Heather Shaw, the national coordinating investigator of this new trial, in a news release.
The new trial follows a successful Phase 2 study which found that this treatment almost halved the risk of cancer recurrence or death after three years in patients with stage IIIB to IV resected melanoma compared with treatment with pembrolizumab alone among patients with advanced melanomas following surgical removal of cancer. Data reported at last year’s American Association of Cancer Research (AACR) congress showed that the regimen achieved a 44% reduction in recurrence or death at 18 months.
Two-year distant metastasis-free survival rates were also presented at AACR, showing a 65% reduction, and the new update indicates this has largely been maintained with a 62% difference at three years.
PHOTO CAPTION:
Medical oncologist Heather Shaw speaks to trial participant Steve Young at the cancer centre earlier this month.
PHOTO CREDIT: Yui Mok/PA
