OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Ensartinib – Ensacove®

DRUG CLASS

Antineoplastic Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NO.	MOLECULAR FORMULA	STRUCTURE
Ensartinib	1370651-20-9	C26-H27-Cl2-FN6-O3

ANNOTATED BIBLIOGRAPHY

References updated: 31 March 2025

Abbreviations: NSCLC, non-small cell lung cancer; ULN, upper limit of the normal range.

• Zimmerman HJ. Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.

  (Review of hepatotoxicity published in 1999 before the availability of tyrosine kinase inhibitors such as ensartinib).
• DeLeve LD. Erlotinib. Cancer chemotherapy. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 556.

  (Review of hepatotoxicity of cancer chemotherapeutic agents discusses several tyrosine kinase inhibitors including imatinib, gefitinib, erlotinib and crizotinib, but not ensartinib).
• Wellstein A, Giaccone G, Atkins MB, Sausville EA. Pathway-targeted therapies: monoclonal antibodies, protein kinase inhibitors, and various small molecules. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 1203-36.

  (Textbook of pharmacology and therapeutics).
• FDA. Integrated Review. 2024. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2025/218171Orig1s000IntegratedR.pdf

  (FDA review of the data on efficacy and safety of ensartinib in support of its approval for NSCLC in the US, mentions that liver test abnormalities were frequent in the 458 patients who received ensartinib, ALT elevations arising in 59%, AST in 58%, Alk P in 51%, and bilirubin in 12%; ALT values rose above 5 times the upper limit of normal (ULN) in 5% of patients and aminotransferase elevations led to dose interruptions in 4.6% and discontinuation in 1.3%, with one instance of suspect drug-induced liver injury but no instances of life-threatening or fatal liver injury).
• Spraggs CF, Xu CF, Hunt CM. Genetic characterization to improve interpretation and clinical management of hepatotoxicity caused by tyrosine kinase inhibitors. Pharmacogenomics 2013; 14: 541-54. [PubMed: 23556451]

  (Review of genetic associations of serum ALT and bilirubin elevations during therapy with tyrosine kinase inhibitors focusing on lapatinib and pazopanib; ensartinib is not discussed).
• Shah RR, Morganroth J, Shah DR. Hepatotoxicity of tyrosine kinase inhibitors: clinical and regulatory perspectives. Drug Saf 2013; 36: 491-503. [PubMed: 23620168]

  (Review of the hepatotoxicity of 18 tyrosine kinase inhibitors approved for use in cancer in the US as of 2013, before the availability of ensartinib which is not discussed).
• Horn L, Infante JR, Reckamp KL, Blumenschein GR, Leal TA, Waqar SN, Gitlitz BJ, et al. Ensartinib (X-396) in ALK-positive non-small cell lung cancer: Results from a first-in-human phase I/II, multicenter study. Clin Cancer Res. 2018;24:2771-2779. [PMC free article: PMC6004248] [PubMed: 29563138]

  (In an open label dose-finding study of ensartinib for advanced, ALK-positive NSCLC, a dose of 225 mg daily was chosen as optimal and subsequently yielded an objective response rate of 60% and acceptable toxicity, including AST elevations in 12% which were above 5 times ULN in only 1% of participants).
• Yang Y, Zhou J, Zhou J, Feng J, Zhuang W, Chen J, Zhao J, et al. Efficacy, safety, and biomarker analysis of ensartinib in crizotinib-resistant, ALK-positive non-small-cell lung cancer: a multicentre, phase 2 trial. Lancet Respir Med. 2020;8:45-53. [PubMed: 31628085]

  (Among 160 adults with advanced, ALK-positive NSCLC with tumor progression after treatment with crizotinib, 52% had an objective response to ensartinib [including 70% of those with brain metastases] with elevations in ALT in 46% which were above 5 times ULN in 6%, but only 2 subjects required drug discontinuation because of liver test abnormalities, and none developed clinically apparent liver injury with jaundice).
• Peng L, Xiao K, Cui J, Ye XH, Zhang YC, Mao L, Selvaggi Get al. Successful treatment with ensartinib after alectinib-induced hyperbilirubinemia in ALK-positive NSCLC. Onco Targets Ther. 2021;14:3409-3415. [PMC free article: PMC8164872] [PubMed: 34079286]

  (56 year old Chinese man with NSCLC developed itching and jaundice 4 months after starting alectinib [bilirubin 18.4 mg/dL, ALT 42 U/L, Alk P 374 U/L], which slowly resolved after stopping and he was later treated with ensartinib with a tumor response and no worsening of bilirubin or liver enzymes).
• Horn L, Wang Z, Wu G, Poddubskaya E, Mok T, Reck M, Wakelee H, et al. Ensartinib vs crizotinib for patients with anaplastic lymphoma kinase-positive non-small cell lung cancer: a randomized clinical trial. JAMA Oncol. 2021;7:1617-1625. [PMC free article: PMC8414368] [PubMed: 34473194]

  (Among 290 patients with advanced ALK-positive NSCLC treated with ensartinib or crizotinib, progression-free survival was 25.8 vs 12.7 months, while adverse event rates were similar including serious events in 7.7% vs 6.1%, drug discontinuations in 9.1% vs 6.8%, the most common adverse events being rash [70% vs 10%] and ALT elevations [50% vs 47%] that were above 5 times ULN in 4.2% vs 7.5%, elevations in liver enzymes being the most frequent reason for drug discontinuation).
• Ensartinib (Ensacove) for non-small cell lung cancer. Med Lett Drugs Ther. 2025;67:e34-e35. [PubMed: 39946703]

  (Concise review of the mechanism of action, clinical efficacy, and safety of ensartinib shortly after its approval for use in the US, mentions hepatotoxicity as an adverse reaction without providing details).