Ensartinib Reduces Recurrence Risk After Resection in ALK-Positive NSCLC

The second-generation ALK inhibitor ensartinib (Ensacove) produced a significant improvement in 24-month disease-free survival (DFS) rate compared with placebo in patients with completely resected stage IB to IIIB ALK-positive non–small cell lung cancer (NSCLC) following adjuvant chemotherapy, according to data from the phase 3 ELEVATE trial (NCT05341583) that were published in The New England Journal of Medicine.^1,2

Patients with stage II to IIIB disease who received ensartinib (n = 103) experienced a 24-month DFS rate of 86.4% compared with 53.5% in the placebo group (n = 102; HR, 0.20; 95% CI, 0.11-0.38; P < .001).² In the overall population, these respective rates were 87.3% and 57.2% in the ensartinib (n = 137) and placebo (n = 137) groups (HR, 0.20; 95% CI, 0.10-0.37; P < .001). Overall survival (OS) data were immature at the time of the publication.

"The publication of the ELEVATE study in [The New England Journal of Medicine] represents high recognition from the international medical community of the scientific value and clinical significance of this research” Ding Lieming, MD, chairman and chief executive officer of Betta Pharmaceuticals, stated in a news release.¹ “It is not only an important milestone for Betta but also a landmark achievement showcasing Chinese clinical oncology research on the global academic stage, with the potential to change postoperative adjuvant treatment strategies for patients with ALK-positive lung cancer.”

Previously, in December 2024, the FDA approved ensartinib for the treatment of adult patients with ALK-positive locally advanced or metastatic NSCLC who had not previously received an ALK inhibitor.³ The regulatory decision was supported by data from the phase 3 eXALT3 trial (NCT02767804), which showed that treatment with ensartinib led to a significant improvement in progression-free survival (PFS) compared with crizotinib (Xalkori; HR, 0.56; 95% CI, 0.40-0.79; P = .0007).

How was ELEVATE designed?

ELEVATE was a multicenter, double-blind trial that enrolled adult patients with histologically confirmed, completely resected stage IB, II, IIIA, or IIIB NSCLC.² Patients were also required to have an ECOG performance status of 0 or 1, have centrally confirmed ALK positivity per immunohistochemistry, and have received adjuvant chemotherapy if they had stage IIB to IIIB disease.

Patients were randomly assigned 1:1 to receive oral ensartinib at 225 mg once daily or placebo following complete surgical resection and any planned adjuvant chemotherapy. Ensartinib or placebo was administered for up to 24 months or until disease recurrence, unacceptable toxicity, or withdrawal of consent.

The primary end point was DFS in patients with stage II to IIIB disease. The key secondary end point was DFS in the overall population; other secondary end points included OS, 3- and 5-year DFS rates, and safety.

What additional ELEVATE data have been recently published?

Among patients with stage II to IIIB disease, the median DFS values were not calculable (NC; 95% CI, not evaluable [NE]-NE) and 24.8 months (95% CI, 22.2-NE) in the investigational and control arms, respectively. In the overall population, these respective values were NC (95% CI, NE-NE) and 24.8 months (95% CI, 22.2-NE). Consistent DFS benefits were reported across nearly all prespecified subgroups in favor of ensartinib.

In terms of safety, any-grade adverse effects (AEs) were reported in 98.5% of patients in the investigational arm and 92.0% of patients in the placebo group. Grade 3 or higher AEs were reported at rates of 35.8% and 18.2%, respectively. Fatal AEs were reported in 1 patient in the ensartinib arm and 2 patients in the placebo arm; none of these fatal AEs were deemed to be related to treatment.

“The marketing application for the adjuvant indication of ensartinib has already been accepted in China,” Lieming added in the news release.¹ “Moving forward, we will continue to focus on unmet clinical needs, deepen independent innovation, and accelerate the development of more innovative products with core competitiveness and global impact, benefiting more patients.”

References

1. Groundbreaking achievement: study of ensartinib as postoperative adjuvant therapy published in The New England Journal of Medicine. News release. Betta Pharmaceuticals. July 8, 2026. Accessed July 9, 2026. https://www.prnewswire.com/news-releases/groundbreaking-achievement-study-of-ensartinib-as-postoperative-adjuvant-therapy-published-in-the-new-england-journal-of-medicine-302821419.html
2. Yue D, Huang M, Song P, et al. Ensartinib in resected ALK-positive non-small-cell lung cancer. N Engl J Med. 2026;395(2):151-161. doi:10.1056/NEJMoa2518990
3. FDA approves ensartinib for ALK-positive locally advanced or metastatic non-small cell lung cancer. FDA. December 18, 2024. Accessed July 9, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ensartinib-alk-positive-locally-advanced-or-metastatic-non-small-cell-lung-cancer