Merck and Moderna report that personalized mRNA therapy with pembrolizumab met two endpoints in a phase III melanoma trial

Merck and Moderna report that personalized mRNA therapy with pembrolizumab met two endpoints in a phase III melanoma trial

On August 19, Merck and Moderna reported results from INTerpath-001, a phase III trial involving 1 137 participants. After complete resection of high-risk melanoma, all participants received pembrolizumab. One group also received individually manufactured intismeran, while the other received a placebo. According to the companies, the combination met two trial endpoints: recurrence-free survival and distant metastasis-free survival.

The risk of melanoma returning remains after surgical removal. Pembrolizumab is an immunotherapy that blocks PD-1, a protein that reduces the activity of T-cells capable of attacking the tumor. Intismeran provides these cells with specific targets. Oncologist Lennard Lee described how the drugs work together in a comment to the Science Media Centre:

“One drug helps the immune system recognize what to look for, while the other releases the brake on the immune response.”

To produce intismeran, researchers take a sample of the individual patient’s tumor, identify its mutations, and select up to 34 neoantigens, which are protein fragments that distinguish cancer cells from healthy cells. The sequences of these fragments are encoded in mRNA. After injection, the patient’s cells produce the fragments and present them to T-cells.

An analysis of target selection for a personalized cancer vaccine explains that HLA proteins on the cell surface must present a mutation fragment to a T-cell. INTerpath-001 does not disclose how targets were selected for each participant, but it tests the outcome of this process: whether personalized mRNA therapy provides additional benefit alongside pembrolizumab.

In INTerpath-001, both groups received pembrolizumab. One group also received intismeran, while the other received a placebo. This comparison measures the contribution of personalized mRNA therapy when both groups receive the same immunotherapy. The primary endpoint was the time to recurrence, disease progression, or death. Another important endpoint was the time to distant metastasis or death.

The trial evaluates the entire process under a single clinical protocol, from sequencing tumor mutations and manufacturing personalized mRNA to comparing the treatment against the same immunotherapy. In an August 19 release, Merck and Moderna reported that the combination met both stated endpoints.