Ensartinib

Xu H, et al. Asian Journal of Surgery, 2024, 47(9), 3947-3949.

Ensartinib was evaluated in ALK-positive NSCLC patients presenting with brain metastases. Four cases were followed in which patients previously treated with crizotinib or radiation therapy were transitioned to oral ensartinib (225 mg once daily). Clinical response was assessed by chest CT and brain MRI, with disease remission defined according to RECIST 1.1 criteria. Imaging was jointly reviewed by radiologists and oncologists to ensure accuracy. Remarkably, significant reduction in intracranial lesions was observed within 3-7 days of treatment initiation, with concurrent alleviation of neurological symptoms such as dizziness and vomiting. In one case, prolonged administration over five months led to cavitary shrinkage of brain lesions. These findings highlight ensartinib's rapid and durable intracranial efficacy, establishing its value as an effective therapeutic option for ALK-mutated NSCLC with central nervous system involvement.

Xia Y, et al. eClinicalMedicine, 2025, 81, 103099.

In the EMBRACE phase II trial, ensartinib, a second-generation tyrosine kinase inhibitor with activity against MET, was evaluated in advanced or metastatic non-small-cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations. Thirty-one patients who had progressed after chemotherapy or immunotherapy were enrolled. Participants received oral ensartinib at 225 mg once daily in continuous 28-day cycles until progression, unacceptable toxicity, or death. Efficacy endpoints included investigator-assessed objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and duration of response (DoR). The study achieved an ORR of 53.3% and DCR of 86.7%, with a median PFS of 6.0 months. Safety monitoring revealed manageable adverse events, primarily rash and hepatic enzyme elevations. Importantly, exploratory circulating tumor DNA (ctDNA) analysis demonstrated that early ctDNA clearance correlated with improved clinical outcomes, underscoring its translational utility as a biomarker.