Abstract
Rigosertib is a panRAS signaling inhibitor that competitively binds to RAS binding domains of downstream effector proteins, resulting in disruption of multiple RAS-mediated pathways (MAPK, PI3K, RalGDS) and tumor suppression in preclinical models. Inhibition of RAS pathways by rigosertib has also been shown to increase tumor immunogenicity. Here we report safety and interim efficacy of the first clinical trial of rigosertib in combination with the immune checkpoint inhibitor (ICI) nivolumab, in advanced KRAS mutated NSCLC patients who progressed on first line ICI-containing treatment.
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