Adjuvant Ensartinib Demonstrates Significant Disease-Free Survival Benefit in ALK-Positive Non-Small Cell Lung Cancer

Clinical Summary: 

• Design/Population: The phase 3 ELEVATE trial evaluated adjuvant ensartinib versus placebo in patients with completely resected stage IB to IIIB ALK-positive non-small cell lung cancer following adjuvant chemotherapy.
• Key Outcomes: Adjuvant ensartinib significantly improved disease-free survival compared with placebo in both the stage II-IIIB and overall study populations. Overall survival data remain immature, and the safety profile was consistent with previous experience with ensartinib.
• Clinical Relevance: These findings support adjuvant ensartinib as a potential treatment option for patients with resected ALK-positive non-small cell lung cancer following chemotherapy.

Results from the phase 3 ELEVATE trial demonstrated that adjuvant ensartinib significantly improved disease-free survival (DFS) compared with placebo in patients with completely resected anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), supporting its use following adjuvant chemotherapy.

“ALK inhibitors have emerged as promising agents for patients with resectable ALK-positive NSCLC,” stated Dongsheng Yue, MD, Tianjin Medical University Institute and Hospital, Tianjin, China, and couathors. “Whether ensartinib, a second-generation ALK inhibitor, is safe and effective in such patients is unknown.” 

In this double-blind trial, 274 patients with completely resected stage IB to IIIB ALK-positive NSCLC who had completed adjuvant chemotherapy were randomized 1:1 to receive either 225 mg of once-daily ensartinib (n = 137) or placebo (n = 137) for 24 months. The primary end point was DFS in patients with stage II to IIIB disease. DFS in the overall study population was a key secondary end point.

Among patients with stage II to IIIB disease, 86.4% of those treated with ensartinib remained alive and disease-free at 24 months compared with 53.5% of those receiving placebo, corresponding to an 80% reduction in the risk of disease recurrence or death (hazard ratio [HR], 0.20; 95% confidence interval [CI], 0.11 to 0.38; P < .001).

The DFS benefit was maintained in the overall study population, with 87.3% of patients receiving ensartinib remaining alive and disease-free at 24 months compared with 57.2% of those receiving placebo (HR, 0.20; 95% CI, 0.10 to 0.37; P < .001). Overall survival data were immature at the time of analysis.

Grade ≥3 adverse events were reported in 35.8% of patients in the ensartinib arm and 18.2% of patients in the placebo arm. Rash was the most frequently reported grade ≥3 adverse event among patients receiving ensartinib.

“Among patients with completely resected stage IB to IIIB ALK-positive NSCLC, the percentage of patients who were alive and disease-free at 24 months was significantly higher with ensartinib than with placebo,” concluded Dr Yue et al. 

Source: 

Yue D, Huang M, Song P, et al. Ensartinib in resected ALK-positive non–small-cell lung cancer. N Engl J Med. Published online: July 8, 2026. doi: 10.1056/NEJMoa2518990