| References: |
KO-947 showed potent inhibition of ERK signaling pathways and proliferation of tumor cells exhibiting dysregulation of MAPK pathway, including mutations in BRAF, NRAS or KRAS. KO-947 also inhibits MAPK signaling and cell proliferation in preclinical models that are resistant to BRAF and MEK inhibitors. Results obtained from screening a large panel of PDX models demonstrate that KO-947 induces tumor regressions in BRAF or RAS mutated tumor models as well as in tumor models lacking BRAF/RAS mutations but characterized by other dysregulation of the MAPK pathway.
KO-947 appears to be differentiated from other published ERK inhibitors by an extended residence time and prolonged pathway inhibition in vitro and in vivo. The data further suggest that the drug properties of KO-947 may allow Kura to maximize the therapeutic window with flexible administration routes and schedules, including intermittent dosing.
KO-947 is currently in a Phase 1 clinical trial in patients with locally advanced unresectable or metastatic, relapsed and/or refractory non-hematological malignancies |
