Consistently, when we tested the intracranial activity of zurletrectinib against mouse glioma orthotopic models harboring 1st-generation TRK inhibitor resistance mutations, we found that zurletrectinib was as efficacious as selitrectinib and repotrectinib against the solvent front single mutant but significantly superior against the Trka G598R/G670A double mutant (Fig. 4). The gene discussed is TPM3; the disease is glioma.