Efficacy and Safety of Ensartinib in the Treatment of Non-Small Cell Lung Cancer: A Systematic Review of Clinical Trials

Anaplastic lymphoma kinase (ALK) rearrangements are the therapeutic targets in non-small cell lung cancer (NSCLC). Ensartinib, a second-generation ALK tyrosine kinase inhibitor (TKI), was recently approved by the FDA for the treatment of ALK-positive NSCLC. In this systematic review, we identified five studies including a total of 621 participants, by searching PubMed, Scopus, and Embase through May 2025. The phase I clinical trials suggested a recommended phase II dose (RP2D) of 225 mg. Ensartinib demonstrated favourable efficacy across dose-escalation, phase II and phase III trials. In treating naïve patients, ORRs ranged from 80–81%, with median PFS reaching up to 26.2 months. In pre-treated cases, efficacy was also notable, including intracranial response upto 70%. Phase III trial confirmed superior PFS with ensartinib compared to crizotinib. Common AEs include rash, transaminase elevations, and gastrointestinal symptoms, which were mostly manageable and grade 1–2 in severity. Ensartinib is a highly effective and tolerable option for ALK-positive NSCLC. Further studies are needed to assess long-term outcomes and to optimize its use in a molecularly diverse patient population.