Ensartinib as a First-line Treatment for NSCLC

Ensartinib as a First-line Treatment for NSCLC
Interim results suggest advantages over crizotinib for ALK-positive disease.

Patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer treated with ensartinib fared better and lived longer than those who received crizotinib, according to interim results of the phase 3 eXalt3 trial.

“Ensartinib showed a significant improvement in progression-free survival compared to crizotinib, much better control of central nervous system disease and a really good safety profile,” said Leora Horn, M.D., Ingram Professor of Cancer Research at Vanderbilt University Medical Center.

Horn presented interim results of the phase 3 study at the International Association for the Study of Lung Cancer World Conference on Lung Cancer Virtual Presidential Symposium.

Comparing as First-line Therapies

Ensartinib and crizotinib are both ALK tyrosine kinase inhibitors. While crizotinib received FDA approval in 2011, ensartinib is a newer targeted therapy that was initially tested and validated at a Vanderbilt by Christine Lovly, M.D., an associate professor of medicine.

Prior phase 1 and phase 2 clinical trials have shown that ensartinib is effective for patients whose cancer has progressed on crizotinib as well as second-generation ALK inhibitors.

The ongoing, randomized, open label phase 3 study compares ensartinib and crizotinib as first-line treatments. Eligibility requirements include no prior ALK inhibitors and up to one prior chemotherapy regimen.

Interim results find that the progression-free survival for ensartinib was double that of crizotinib (25.8 months compared to 12.7 months). The time-to-treatment failure rate in the brain of patients with no baseline brain metastases was significantly lower with ensartinib, 4 percent at 12 months compared to 24 percent for crizotinib.

Expanding Treatments Options

Approximately 5 to 7 percent of patients with non-small cell lung cancer have the ALK-positive form of disease, which often occurs in younger people and has no known correlation to smoking or environmental toxins.

“We hope that ensartinib will be another drug that receives FDA approval for patients who are ALK positive,” Horn said.

“We hope that ensartinib will be another drug that receives FDA approval for patients who are ALK positive.”

The eXalt3 study is estimated to conclude in March 2021, at which point the impact of ensartinib on overall survival will be assessed.