By Mukundan Sivaraj · AIM Media House
Merck and Moderna announced positive topline results on August 19 from a Phase 3 trial testing a personalized cancer vaccine, formally known as an individualized neoantigen therapy (INT), alongside the checkpoint drug KEYTRUDA in melanoma patients whose tumors had already been surgically removed.
The companies say it is the first positive Phase 3 trial of an INT and of any mRNA-based cancer therapy. The therapy at the center of the trial, intismeran autogene, is built differently from a standard drug.
Instead of one fixed formula, an algorithm helps select each patient's specific targets, based on their own tumor. How The Algorithm Selects The Vaccine's Targets Making intismeran starts with a sample of a patient's tumor and blood, sequenced to map its mutations.
Moderna says a series of AI algorithms then reviews those mutations and predicts which resulting proteins, known as neoantigens, are most likely to trigger an immune response. Up to 34 of the top-ranked neoantigens are encoded onto a single strand of mRNA, wrapped in a lipid nanoparticle, and given to the patient.
The vaccine plays a different role from checkpoint drugs alone, says Diwakar Davar, vice chief of academic affairs at UPMC Hillman Cancer Center's melanoma program. "The drug works by augmenting DCs which aren't licensed by checkpoint blockade," Davar said to AIM Media House .
KEYTRUDA works by blocking PD-1 signaling, which increases the immune system's ability to detect and fight tumor cells that it can already recognize.
Davar's point is that the vaccine adds something upstream of that: it activates dendritic cells, the immune system's scouts, to help generate new tumor-specific T-cell responses in the first place.
What The Trial Showed, And What Is Still Unknown INTerpath-001 enrolled 1,137 patients with completely resected Stage IIB to IV melanoma, none of whom had received prior systemic treatment.
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