Ensartinib (X-396) in ALK-positive non–small cell lung cancer: Results from a first-in-human phase I/II, multicenter study

Leora Horn, Jeffrey R. Infante, Karen L. Reckamp, George R. Blumenschein, Ticiana A. Leal, Saiama N. Waqar, Barbara J. Gitlitz, Rachel E. Sanborn, Jennifer G. Whisenant, Liping Du, Joel W. Neal, Jon P. Gockerman, Gary Dukart, Kimberly Harrow, Chris Liang, James J. Gibbons, Allison Holzhausen, Christine M. Lovly, Heather A. Wakelee

Research output: Contribution to journalArticlepeer-review

147 Scopus citations


Purpose: 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). Patients and Methods: 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 ALK-positive NSCLC were administered 225 mg once daily. Patients who had received prior ALK TKI(s) and patients with brain metastases were eligible. Results: 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 ALK-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-na€ve 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%. Conclusions: Ensartinib was active and generally well tolerated in patients with ALK-positive NSCLC.

Original languageEnglish
Pages (from-to)2771-2779
Number of pages9
JournalClinical Cancer Research
Issue number12
StatePublished - Jun 15 2018


Dive into the research topics of 'Ensartinib (X-396) in ALK-positive non–small cell lung cancer: Results from a first-in-human phase I/II, multicenter study'. Together they form a unique fingerprint.

Cite this