To identify the determinants of response and resistance to RET inhibitor therapy in patients with RET-dependent cancers, we characterized pre-treatment and post-progression tumor biopsies and plasma cell-free DNA (cfDNA) specimens collected from 72 patients treated with the selective RET inhibitor selpercatinib on LIBRETTO-001, a registrational phase 1/2 trial (see “Methods”, Supplemental Fig. 1). The gene discussed is RET; the disease is cancer.