Introduction
Dysfunction of the mesenchymal epithelial, tumor
TUMOR GROWTH, SOLID TUMORS, TUMORIGENESIS, TUMOR
Dysfunction of the mesenchymal epithelial transition (MET) tyrosine kinase receptor and the MET pathway through Besides its role in tumorigenesis, the MET pathway is known to have immune regulatory functions, amongst others through the upregulation of indoleamine-2,3-dioxygenase (IDO), an immunosuppressive enzyme. IDO catalyzes the degradation of tryptophan to kynurenin. Depletion of tryptophan leads to decreased differentiation of immune cells, while the metabolic intermediate kynurenin inhibits immune cell function.OMO-1 is a highly potent, orally bioavailable dual MET kinase/OCT-2 inhibitor. In preclinical studies, OMO-1 leads to complete inhibition of tumor growth in diverse in vivo MET-activated tumor models.Here we describe a phase I study to establish the safety and preliminary efficacy of the dual MET kinase/OCT-2 inhibitor OMO-1 in patients with solid tumors refractory to standard treatment and, subsequently, in patients with MET-positive solid tumors.Trial registration: Clinicaltrials.gov registry number NCT03138083.