In three Phase I/II trials, Eransertinib potently blocked TRKA/B/C and ROS1, resulting in deep (objective response rate 57.4%) and long-lasting (median DoR 10.4 months) responses in adults with NTRK fusions. The post adds to previous findings by revealing additional patients and longer follow-up. Patients with locally advanced/metastatic NTRK fusions-positive solid tumors and a minimum of 12 months’ follow-up were enrolled. The primary endpoints were ORR and DoR, which were assessed by an independent central review (BICR); secondary endpoints included PFS, intracranial efficacy, and safety. All patients who had been given at least one entrectinib dose were included in the safety-evaluable group. The efficacy-evaluable population, as of August 31, 2020, included 121 individuals with 14 different types of cancer and at least 30 histological subtypes. The median follow-up was 25.8 months, with 61.2% of patients achieving a complete (n = 19) or partial response (n = 55). The median duration of progression-free survival (DoR) was 20.0 months (95% CI, 13.0–38.2), with a median PFS of 13.8 months (95% CI, 10.1–19.9). In 11 individuals with BICR-diagnosed measurable central nervous system (CNS) disease, intracranial ORR was 63.6% (95% CI, 30.8–89.1), and median intracranial DoR was 22.1 months (95% CI, 7.4–not estimable). The safety profile of entrectinib in adults and children was comparable to that reported previously. The majority of treatment-related adverse events (TRAEs) were grade 1/2 and resolved or reversible with adjustments to the dosage. About 8.3% of persons who took AZD simple experienced TETRAE-related drug withdrawals. With greater clinical data, entrectinib continues to show systemic and intracerebral responses that are both durable and effective in patients with NTRK fusion-positive solid tumors who do not respond adequately to standard therapy.