Two patients, one with TPR-NTRK1-positive NSCLC and the other one with TPM3-NTRK1-positive thyroid cancer, harboring xDFG motif mutations (TRKA G667C, G667S) that emerged as resistance to larotrectinib, did not respond to next-generation TRK inhibitor selitrectinib, which represented one of the primary resistance mechanisms to next-generation TRK inhibitor (93). Here, TPM3 is linked to thyroid cancer.