Stably transfected NIH-3T3 ΔTRKA and ΔTRKA-G595R cells are implanted subcutaneously into the flanks of nude mice. Both larotrectinib and Selitrectinib (LOXO-195) are effective at reducing phosphorylated TRKA in tumors driven by ΔTRKA. In contrast, only Selitrectinib (LOXO-195) strongly suppresses phospho-TRKA in ΔTRKA-G595R cells in a dose-dependent manner. Selitrectinib (LOXO-195) also causes inhibition of tumor growth relative to vehicle at all doses in four TRKA-dependent tumor models (ΔTRKA, ΔTRKA-G595R, ΔTRKAG667C, and TPM3-NTRK1 fusion-positive KM12 colorectal cancer cells. Larotrectinib inhibits KM12 and NIH 3T3-ΔTRKA tumors to a similar degree. Group mean body weight loss does not exceed 5% for any agent. Selitrectinib (LOXO-195) displays high selectivity for the TRK proteins[1]