Cancer

Cell culture and mouse studies suggest inhibiting AURKA, AURKB and AURKC could enhance the efficacy of T790M-mutant EGFR inhibitors against EGFR-mutant NSCLC. Screening of 94 compounds against cancer pathway targets in a human NSCLC cell-based growth assay identified a tool compound AURKB inhibitor and a pan-Aurora kinase tool inhibitor that exhibited the greatest synergistic inhibition of growth in combination with the T790M-mutant EGFR inhibitor rociletinib. In four human NSCLC cell lines expressing EGFR mutations, the AURKA inhibitor alisertib plus rociletinib or Tagrisso osimertinib decreased growth compared with any agent alone. In an EGFR T790M-mutant, patient-derived xenograft (PDX) mouse model of NSCLC, alisertib plus rociletinib decreased tumor growth compared with either agent alone. Next steps include testing undisclosed Aurora kinase inhibitors in patients with EGFR-mutant NSCLC who have progressed on Tagrisso.

Takeda Pharmaceutical Co. Ltd. has alisertib in Phase II testing for B cell lymphoma, breast cancer, head and neck cancer, non-Hodgkin lymphoma, NSCLC and ovarian cancer and Phase I testing for solid tumors...