Ensartinib, a new generation anaplastic lymphoma kinase (ALK) inhibitor, was found to be both safe and efficacious in patients with ALK-positive non-small cell lung cancer (NSCLC) who previously failed treatment with crizotinib, according to phase 2 study findings.

The single-arm, open-label, multicenter study conducted in China aimed to evaluate the safety and efficacy of ensartinib as well as the relationship between its efficacy and crizotinib-resistant mutations. Patients included in the study were ≥18 years old with measurable disease that had stage IIIB or IV ALK-positive NSCLC that progressed despite receiving treatment with crizotinib. Patients were also required to have received <3 treatments previously as well as an Eastern Cooperative Oncology Group performance status of ≤2. Additionally, patients with CNS metastases were included in the study only if the metastases did not require steroid therapy and were asymptomatic. 

During the study, each patient received ensartinib 225mg daily. “The primary outcome was the proportion of patients with an objective response according to the Response Evaluation Criteria in Solid Tumors (version 1.1), as assessed by an independent review committee in all patients who received at least 1 dose of ensartinib with no major violations of the inclusion criteria (ie, the full analysis set),” the authors explained. All patients who received ≥1 dose of ensartinib were included in the safety assessment. 

A total of 160 patients were included in the safety analysis (safety analysis set) while 156 were included in the efficacy analysis (full analysis set). Of the total patients in the full analysis set, 62% (n=97) had brain metastases. The study authors reported that 52% (76/147; 95% CI: 43, 60) of patients in the full analysis set had an objective response while 70% (28/40; 95% CI: 53, 83) of patients with measurable brain metastases had an intracranial objective response. 


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Analysis of the safety data determined that 91% (145/160) of patients experienced ≥1 treatment-related adverse event. The majority of treatment-related adverse events were considered grade 1 or 2 with the most commonly reported events being rash (56%), elevated alanine aminotransferase concentrations (46%), and elevated aspartate aminotransferase concentrations (41%). 

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“Ensartinib has activity and is well tolerated in patients with crizotinib-refractory, ALK-positive NSCLC, including those with brain metastases,” the study authors concluded. They added, “The role of ensartinib in patients in whom other second-generation ALK inhibitors have been unsuccessful warrants further studies.”

For more information visit thelancet.com.