NHS UK Foundation Trust

mRNA vaccine for melanoma recurrence prevention advances to phase 3 testing

April 30, 2024

A new study led by University College London Hospitals NHS Foundation Trust (UCLH) has begun enrolling participants with the aim to evaluate the combination of mRNA-4157 (also known as V940) and pembrolizumab compared with the current standard of care (pembolizumab alone) in reducing risk in patients with resected, high-risk, stage IIB to IV melanoma.

The phase 3 global, randomized, double-blind, placebo- and active-comparator-controlled study (named INTerpath-001) will enroll 1,089 patients from across the world.

An earlier phase 2 study—KEYNOTE-942—released in January found that in patients with stage IIIB to IV resected melanoma this treatment option resulted in a 49% reduction in the risk of cancer recurrence or death after three years compared with treatment with pembrolizumab alone among patients with advanced melanomas following surgical resection.

Known as mRNA-4157 (V940), the neoantigen therapy individualized for each patient works by directing the body to make up to 34 proteins, each targeting tumor 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. A sample of tumor is removed during the patient’s surgery, followed by DNA sequencing and the use of AI. The result is a custom-built, anti-cancer vaccine that's specific to the patient’s tumor.

Melanoma rates have been increasing over the past few decades, with nearly 325,000 new cases diagnosed worldwide in 2020.

Sources:

(2024, April 26). NHS. University College London Hospitals. NHS Foundation Trust. First patients getting individualized risk-reducing therapy. https://www.uclh.nhs.uk/news/first-patients-getting-individualised-risk-reducing-therapy-melanoma

Weber JS, et al. (2024, February 17). Lancet. Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study. https://pubmed.ncbi.nlm.nih.gov/38246194/