IO Biotech’s cancer vaccine Cylembio, tested in combination with Merck’s Keytruda for unresectable or metastatic melanoma, narrowly failed to meet its primary progression-free survival endpoint in a global Phase 3 trial. The hazard ratio did not reach statistical significance with a P value just above the required threshold. However, subgroup analyses showed promising effects, particularly in patients without prior anti-PD-1 treatment. Despite the setback, IO Biotech plans to engage the FDA to seek approval discussions based on the totality of data and observed survival trends. This off-the-shelf vaccine approach targets tumor immune checkpoints PD-L1 and IDO1, differing from personalized mRNA cancer vaccines.