*February 2021*

Highlights from Dr. Collin Blakely’s presentation: EGFR TKI Combination Therapies: C797S, MEK, AURORA Kinase at the 2021 Targeted Therapies Conference:

  • EGFR C797S is the predominant on-target resistance mutation
  • Osimertinib + gefitinib prevents acquired second-site EGFR resistance mutations in preclinical models
  • 1 st line Osimertinib + Gefitinib is well-tolerated with ~ 90% ORR
  • 4 th Generation EGFR Inhibitors (BLU-945) can target both T790M and C797S
  • Limited activity of osimertinib + selumetinib after 3rd gen. EGFR TKI
  • ~ 60% of resistance to 1st line osimertinib remains undefined
  • Aurora kinase A drives the evolution of resistance to thirdgeneration EGFR inhibitors in lung cancer
  • Activation of Aurora Kinase A is an early pro-tumor cell survival mechanism induced by EGFR TKI treatment
  • Aurora kinase A inhibitor alisertib overcomes resistance to osimertinib in PDX models of EGFR lung cancer

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