FDA Approves Ensartinib for ALK-Positive Lung Cancer

On December 18, 2024, the Food and Drug Administration (FDA) granted approval for ensartinib, marketed as Ensacove by Xcovery Holdings, Inc., for use in adult patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) that is either locally advanced or metastatic. This approval is specifically for patients who have not previously undergone treatment with an ALK inhibitor. Detailed prescribing information for Ensacove will be available on the FDA’s Drugs website.

The approval of ensartinib was based on data from the eXALT3 clinical trial (NCT02767804). This study was an open-label, randomized, active-controlled, multicenter trial involving 290 participants with ALK-positive NSCLC, none of whom had received prior ALK-targeted therapy. Participants were divided into two groups with a 1:1 ratio to receive either ensartinib or crizotinib.

The primary measure of effectiveness in the study was progression-free survival (PFS), evaluated by a blinded independent central review. A key secondary endpoint was overall survival (OS). Ensartinib demonstrated a significant improvement in PFS compared to crizotinib, with a hazard ratio of 0.56 (95% CI: 0.40, 0.79; p-value 0.0007). The median PFS for patients in the ensartinib group was 25.8 months (95% CI: 21.8, not estimable), whereas it was 12.7 months (95% CI: 9.2, 16.6) for those in the crizotinib group. In terms of overall survival, there was no significant difference between the two groups, as indicated by a hazard ratio of 0.88 (95% CI: 0.63, 1.23; p-value 0.4570).

Among the most common side effects observed in 20% or more of the patients receiving ensartinib were rash, musculoskeletal pain, constipation, cough, itching, nausea, swelling, fever, and fatigue. These adverse reactions are important considerations for healthcare providers when prescribing this medication.

For the administration of ensartinib, the recommended dosage is 225 mg taken orally once daily. It can be consumed with or without food and should be continued until the patient experiences either disease progression or unacceptable toxicity.

Healthcare professionals are encouraged to report any serious adverse events potentially associated with the use of ensartinib or any other medication to the FDA’s MedWatch Reporting System. This can be done through their website or by calling 1-800-FDA-1088.

In cases where there is a need for single-patient Investigational New Drug applications (INDs) for investigational oncology products, healthcare professionals can reach out to the FDA’s Oncology Center of Excellence’s Project Facilitate for assistance.

This approval of ensartinib provides a new therapeutic option for patients with ALK-positive NSCLC, offering a significant advancement in their treatment journey by potentially extending the period during which the disease does not progress.