Objective

Anaplastic lymphoma kinase (ALK) rearrangements are one of the key 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. This systematic review aims to evaluate the efficacy and safety of ensartinib in adult patients with ALK-positive NSCLC.

Data sources

In this systematic review, we identified five studies including a total of 621 participants, by searching PubMed, Scopus, and Embase from January 2010 to May 2025. We included clinical trials on adult NSCLC patients receiving ensartinib monotherapy or combination therapy, assessing treatment response and safety, and excluded observational studies, brief reports, protocols, and conference abstracts. Study quality was assessed using the MINORS and RoB 2 tools. Results were synthesized qualitatively, providing a comprehensive overview of efficacy and safety outcomes.

Data summary

Our comprehensive synthesis of the included studies revealed favorable outcomes. 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 up to 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.

Conclusion

Ensartinib is a highly effective and tolerable option for ALK-positive NSCLC. However, limitations include the open-label nature of most included studies and the descriptive synthesis, precluding formal meta-analysis and assessment of certainty of evidence. Further studies are needed to assess long-term outcomes and to optimize its use in a molecularly diverse patient population. This review received no specific funding. The protocol was not registered.