On December 18, 2024, the U.S. Food and Drug Administration (FDA) approved the anaplastic lymphoma kinase (ALK) inhibitor ensartinib (Ensacove) for adults with ALK-positive locally advanced or metastatic non–small cell lung cancer (NSCLC) who have not previously received an ALK inhibitor. For full prescribing information on ensartinib, visit Drugs@FDA.
Efficacy and Safety
Efficacy was evaluated in eXALT3 (ClinicalTrials.gov identifier NCT02767804), an open-label, randomized, active-controlled, multicenter trial in 290 patients with locally advanced or metastatic ALK-positive NSCLC who had not previously received an ALK-targeted therapy. Patients were randomly assigned 1:1 to receive ensartinib or crizotinib (a multitargeted small-molecule tyrosine kinase inhibitor).
The main efficacy outcome measure was progression-free survival as evaluated by blinded independent central review. The key secondary efficacy outcome measure was overall survival. Ensartinib demonstrated a statistically significant progression-free survival improvement compared with crizotinib, with a hazard ratio (HR) of 0.56 (95% confidence interval [CI] = 0.40–0.79; P = .0007). The median progression-free survival was 25.8 months (95% CI = 21.8 months to not estimable) with ensartinib and 12.7 months (95% CI = 9.2–16.6 months) with crizotinib. There was no statistically significant difference in overall survival (HR = 0.88 [95% CI = 0.63–1.23], P = .4570).
The most common adverse reactions (≥ 20%) were rash, musculoskeletal pain, constipation, cough, pruritus, nausea, edema, pyrexia, and fatigue.
The recommended dose of ensartinib is 225 mg orally once daily, with or without food, until disease progression or unacceptable toxicity.
