Ensartinib (X-396) in ALK-Positive Non-Small Cell Lung Cancer: Results from a First-in-Human Phase I/II, Multicenter Study.

Horn L, Infante JR, Reckamp KL, Blumenschein GR, Leal TA, Waqar SN, Gitlitz BJ, Sanborn RE, Whisenant JG, Du L, Neal JW, Gockerman JP, Dukart G, Harrow K, Liang C, Gibbons JJ, Holzhausen A, Lovly CM, Wakelee HA
Clin Cancer Res. 2018 24 (12): 2771-2779

PMID: 29563138 · PMCID: PMC6004248 · DOI:10.1158/1078-0432.CCR-17-2398

Evaluate safety and determine the recommended phase II dose (RP2D) of ensartinib (X-396), a potent anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), and evaluate preliminary pharmacokinetics and antitumor activity in a first-in-human, phase I/II clinical trial primarily in patients with non-small cell lung cancer (NSCLC). In dose escalation, ensartinib was administered at doses of 25 to 250 mg once daily in patients with advanced solid tumors; in dose expansion, patients with advanced -positive NSCLC were administered 225 mg once daily. Patients who had received prior ALK TKI(s) and patients with brain metastases were eligible. Thirty-seven patients enrolled in dose escalation, and 60 enrolled in dose expansion. The most common treatment-related toxicities were rash (56%), nausea (36%), pruritus (28%), vomiting (26%), and fatigue (22%); 23% of patients experienced a treatment-related grade 3 to 4 toxicity (primarily rash and pruritus). The maximum tolerated dose was not reached, but the RP2D was chosen as 225 mg based on the frequency of rash observed at 250 mg without improvement in activity. Among the -positive efficacy evaluable patients treated at ≥200 mg, the response rate (RR) was 60%, and median progression-free survival (PFS) was 9.2 months. RR in ALK TKI-naïve patients was 80%, and median PFS was 26.2 months. In patients with prior crizotinib only, the RR was 69% and median PFS was 9.0 months. Responses were also observed in the central nervous system, with an intracranial RR of 64%. Ensartinib was active and generally well tolerated in patients with -positive NSCLC. .

©2018 American Association for Cancer Research.

MeSH Terms (29)

Adult Aged Aged, 80 and over Anaplastic Lymphoma Kinase Animals Antineoplastic Agents Carcinoma, Non-Small-Cell Lung Cell Line, Tumor Disease Models, Animal Dose-Response Relationship, Drug Female Humans Immunohistochemistry In Situ Hybridization, Fluorescence Kaplan-Meier Estimate Lung Neoplasms Male Mice Middle Aged Mutation Neoplasm Grading Neoplasm Staging Piperazines Prognosis Protein Kinase Inhibitors Pyridazines Rats Treatment Outcome Young Adult

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