ELEVATE

Background

Phase 3, double-blind, randomized trial in 274 patients (137 per arm) with completely resected, stage IB-IIIB ALK-positive NSCLC after adjuvant chemotherapy. Ensartinib is a second-generation ALK tyrosine kinase inhibitor.

Results

Interventions and follow up: Arm A: Ensartinib 225 mg PO once daily for 24 months
Arm B: Placebo for 24 months
Primary endpoint: Disease-free survival in stage II-IIIB disease; key secondary DFS in the overall population
mFollow up: 24-month landmark analysis
Results: DFS (stage II-IIIB, 24-mo alive and disease-free): 86.4% vs 53.5%; HR 0.20 (0.11-0.38); P<.001
DFS (overall population): 87.3% vs 57.2%; HR 0.20 (0.10-0.37); P<.001
OS: NR (immature)

Adverse events

Grade ≥3 (any): 35.8% vs 18.2%
Most common: rash (ensartinib)

Conclusions

Adjuvant ensartinib for 24 months reduced the risk of recurrence or death by 80% versus placebo (HR 0.20) after resection and chemotherapy in ALK-positive NSCLC. Overall survival remains immature, but disease-free survival benefit is substantial and consistent across the overall population.

Key Limitations

Overall survival immature; disease-free survival is a surrogate endpoint; enrollment entirely in China (Betta Pharmaceuticals) limits generalizability; optimal treatment duration beyond 24 months is unknown; no head-to-head comparison with alectinib.

Clinical Context

Adjuvant alectinib (ALINA) is FDA-approved (April 2024) and the established adjuvant ALK TKI standard (DFS HR 0.24). ELEVATE shows ensartinib delivers a similar DFS magnitude (HR 0.20) versus placebo after chemotherapy, providing another adjuvant ALK-TKI option, most immediately relevant in China. NCCN and ASCO endorse an adjuvant ALK TKI for resected ALK-positive NSCLC.

References