Osimertinib (TAGRISSO™) and the cobas® EGFR Mutation Test v2

Osimertinib (TAGRISSO) is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, selective for sensitizing and resistance mutations in the receptor. It was initially developed for second and later line use in patients whose disease had progressed on an earlier generation inhibitor due to the acquisition of the T790M resistance mutation. To identify patients whose tumor had acquired T790M-positive resistance, a companion diagnostic was codeveloped alongside the small molecule. The Roche cobas EGFR Mutation Test v2 was developed and clinical utility of T790M mutation detection was demonstrated for osimertinib; the test was initially approved for use with formalin-fixed paraffin-embedded tissue and later with circulating tumor DNA (ctDNA) from plasma samples. Several challenges were overcome to enable simultaneous FDA approval of the companion diagnostic and the new drug application as well as the approval of a plasma ctDNA-based companion diagnostic the following year; these are discussed.