ABOVE: ©ISTOCK, MELETIOS VERRAS
Last April, Merck and Incyte released the discouraging results of a large Phase 3 clinical study testing the combination of two immunotherapies—a promising IDO1 inhibitor and an anti-PD-1 checkpoint blockade therapy—in patients with advanced melanoma. Researchers have shown the anti-PD-1 drug, which blocks a critical inhibitory signal on T cells, to be successful at treating a growing list of cancer types, including melanoma, lung, and bladder. The IDO1 inhibitor targets an enzyme in a metabolic pathway that was shown in preclinical studies to regulate immune function and promote cancer immune escape. But the combination treatment showed no improved benefit over anti-PD-1 therapy on its own.
Due to this disappointing finding, several companies with multibillion-dollar investments scaled back efforts in IDO1-based immunotherapy or decided to halt such efforts altogether, and many started to question the enzyme’s potential as a therapeutic target. But rather than turn our backs ...
