FDA Approves Ensartinib for Locally Advanced or Metastatic ALK+ NSCLC

FDA

The FDA has approved ensartinib (Ensacove) for the treatment of adult patients with ALK-positive locally advanced or metastatic non–small cell lung cancer (NSCLC) who have not previously received an ALK inhibitor.¹

Ensartinib was evaluated in the randomized, open-label, phase 3 eXALT3 (NCT02767804) trial, in which 290 patients with locally advanced or metastatic ALK-positive NSCLC who had not previously received an ALK-targeted therapy were randomly assigned 1:1 to receive ensartinib or crizotinib (Xalkori).

The primary end point was progression-free survival (PFS) according to blinded independent central review. The key secondary end point was overall survival (OS).² The results showed a statistically significant improvement in PFS compared with crizotinib (HR, 0.56; 95% CI, 0.40-0.79; P = .0007).¹ The median PFS was 25.8 months (95% CI, 21.8-not estimable) in the ensartinib arm vs 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 = .4570).

The most common adverse effects that occurred in at least 20% of patients were rash, musculoskeletal pain, constipation, cough, pruritis, nausea, edema, pyrexia, and fatigue.

The multi-center eXALT3 trial enrolled patients at 120 centers across 21 countries between July 25, 2016, and November 12, 2018.² The study included adult patients with advanced, recurrent, or metastatic ALK-positive NSCLC, as determined by local testing. Patients were required to have measurable disease per RECIST v1.1 criteria. Up to 1 prior line of chemotherapy for metastatic disease was allowed, and those with asymptomatic brain metastases were permitted to enroll.

Key exclusion criteria included cancer therapy within 4 weeks or radiotherapy within 14 days of study entry; and prior treatment with ALK TKIs or anti–PD-1/PD-L1 therapy.

Patients were randomly assigned to receive 225 mg of ensartinib once daily or 250 mg of crizotinib twice daily.

Other secondary end points included systemic and intracranial response and time to central nervous system progression. Efficacy was evaluated in the intention-to-treat population and a prespecified, modified ITT (mITT) population that included patients with central laboratory–confirmed ALK-positive NSCLC.

References

1. FDA approves ensartinib for ALK-positive locally advanced or metastatic non-small cell lung cancer. FDA. December 18, 2024. Accessed December 18, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ensartinib-alk-positive-locally-advanced-or-metastatic-non-small-cell-lung-cancer
2. eXalt3: study comparing X-396 (ensartinib) to crizotinib in ALK positive non-small cell lung cancer (NSCLC) patients. ClinicalTrials.gov. Updated August 20, 2024. Accessed December 18, 2024. https://clinicaltrials.gov/study/NCT02767804