On December 18, 2024, the Food and Drug Administration approved ensartinib (Ensacove, Xcovery Holdings, Inc.) for adult patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) who have not previously received an ALK-inhibitor.

Efficacy and Safety

Efficacy was evaluated in eXALT3 (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 randomized 1:1 to receive ensartinib or crizotinib.

The main efficacy outcome measure was progression-free survival (PFS) as evaluated by blinded independent central review. The key secondary efficacy outcome measure was overall survival (OS). Ensartinib demonstrated a statistically significant PFS improvement compared to crizotinib with a hazard ratio (HR) of 0.56 (95% CI: 0.40, 0.79; p-value 0.0007). The median PFS was 25.8 months (95% CI: 21.8, not estimable) in the ensartinib arm and 12.7 months (95% CI: 9.2, 16.6) in the crizotinib arm. There was no statistically significant difference in OS (HR 0.88 [95% CI: 0.63, 1.23], p-value 0.4570).

The most common adverse reactions (≥20%) were rash, musculoskeletal pain, constipation, cough, pruritis, nausea, oedema, pyrexia, and fatigue.

Source: FDA