For First-Line Treatment of ALK-Positive NSCLC

Ensartinib is a potential best-in-class compound for the first-line treatment of anaplastic lymphoma kinase (ALK)–positive non-small cell lung cancer (NSCLC)1

  • Ensartinib has shown promising clinical activity in patients with ALK-positive NSCLC in a phase 1/2 trial2
  • A single-arm phase 2 trial of ensartinib as second-line treatment for patients with ALK-positive NSCLC previously treated with crizotinib has been completed in 156 Chinese patients, and a New Drug Application has been filed in China3
  • An ensartinib global first-line phase 3 registration trial vs crizotinib is ongoing3
Ensartinib MOA diagram

AKT, protein kinase B; ALK, anaplastic lymphoma kinase; JAK3, Janus kinase 3; mTOR, mechanistic target of rapamycin; MOA, mechanism of action; PI3K, phosphoinositide 3-kinase; RAS, MEK, ERK, mitogen-activated protein kinase pathway; STAT3, signal transducer and activator of transcription 3.

References

  1. Lovly CM, et al. Cancer Res. 2011;71:4920-4931.
  2. Horn L, et al. Clin Cancer Res. 2018;24:2771-2779.
  3. Xcovery, Betta Pharmaceuticals. Data on file.

Clinical Trials

Ensartinib pipeline

ALK, anaplastic lymphoma kinase; NDA, new drug application; NSCLC, non-small cell lung cancer; ROS1, ROS proto-oncogene 1, receptor tyrosine kinase.

aIn China

NCT02767804: eXalt3 is a phase 3, randomized study comparing ensartinib with crizotinib in patients with anaplastic lymphoma kinase (ALK)–positive NSCLC.

NCT03215693: This is a phase 2, multicenter, single-arm study in which the safety and efficacy of ensartinib will be assessed in adult Chinese patients with ALK-positive (rearrangement) NSCLC previously treated with crizotinib. NDA filed in China.

NCT03608007: This is a phase 2, multicenter, single-arm study in which the efficacy and safety of ensartinib will be assessed in adult Chinese patients with ROS1-positive (rearrangement or inversion) NSCLC.

NCT01625234: eXalt2 is a phase 1/2, first-in-human dose-escalation study of ensartinib in patients with advanced solid tumors, with an expansion phase in patients with ALK-positive NSCLC.

For more information on ensartinib clinical trials, please contact .

Publications and Abstracts

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.

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(12):2771-2779.

Singhi EK, Horn L.

Background and rationale of the eXalt3 trial investigating X-396 in the treatment of ALK+ non-small-cell lung cancer. Future Oncol. 2018; 14(18):1781-1787.

2019 ELCC
April 10-13, 2019; Geneva, Switzerland

Horn L, Whisenant JG, Wakelee H, L Reckamp KL, Qiao H, Du L, Hernandez J, Huang V, Waqar SN, Patel S, Sanborn RE, Shaffer T, Garg K, Holzhausen A, Harrow K, Liang C, Lim LP, Li M, Lovely CM.

Circulating tumor (ct) DNA analysis to monitor response and resistance to ensartinib in patients (pts) with ALK+ non-small cell lung cancer (NSCLC). Ann. Oncol. 2019;30 (suppl 2):ii44. [abstract 112O]

2018 ESMO Congress
October 19-23, 2018; Munich, Germany

Horn L, Wu Y-L, Reck M, Wakelee H, Liang C, Harrow K, Oertel V, Mok T.

eXalt3: phase III randomized study comparing ensartinib to crizotinib in anaplastic lymphoma kinase positive non-small cell lung cancer patients. Ann Oncol. 2018;29(suppl 8):viii543 [abstract 1500TiP].

Wakelee H, Reckamp KL, Leal TA, Patel SP, Blumenschein G, Shum E, Nieva J, Oxnard G, Sanborn RE, Waqar S, Zeman K, Dukart G, Harrow K, Liang C, Holzhausen A, Horn L.

Intracranial activity of ensartinib in patients with anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC). Ann Oncol. 2018;29(suppl 8):viii541 [abstract 1496P].

IASLC 19th World Conference on Lung Cancer
September 23-26, 2018; Toronto, ON, Canada

Horn L, Wu Y, Reck M, Wakelee H, Liang C, Harrow K, Oertel V, Mok T.

eXalt3: phase 3 randomized study comparing ensartinib to crizotinib in anaplastic lymphoma kinase positive non-small cell lung cancer patients. J Thorac Oncol. 2018;13(10 suppl):S582 [abstract P1.13-02].

Horn L, Patel S, Waqar S, Blumenschein G, Harrow K, Holzhausen A, Liang C, Dukart G, Wakelee H.

Ensartinib treatment beyond disease progression in stage IV ALK+ non-small cell lung cancer. J Thorac Oncol. 2018;13(10 suppl):S583 [abstract P1.13-03].

2018 ASCO Annual Meeting
June 1-5, 2018; Chicago, IL

Horn L, Wu Y-L, Reck M, Wakelee HA, Liang C, Tan F, Harrow K, Oertel V, Dukart G, Mok T.

eXalt3: phase 3 randomized study comparing ensartinib to crizotinib in anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients. J Clin Oncol. 2018;36(15 suppl) [abstract TPS9115].

Fang W, Ma Y, Huang J, Zhang Y, Zou B, Zhao H, Yang Y, Huang Y, Zhao J, Ding L, Tan F, Zhang L.

Ensartinib (X-396), a second-generation ALK TKI, in Chinese ALK-positive non-small cell lung cancer: a phase I, dose-escalation study. J Clin Oncol. 2018;36(15 suppl) [abstract e21122].

2018 ELCC
April 11-14, 2018; Geneva, Switzerland

Horn L, Wu Y-L, Reck M, Liang C, Tan F, Harrow K, Oertel V, Dukart G, Mok TSK.

eXalt3: phase 3 randomized study comparing ensartinib to crizotinib in anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients. J Thorac Oncol. 2018;13(4 suppl):S116 [abstract 194TiP].

IASLC 18th World Conference on Lung Cancer
October 15-18, 2017; Yokohama, Japan

Zhang L, Li J, Zhong W, Hu Y, Liu X, Wang Z, Zhao Y, Feng J, Zhou J, Zhang Y, Fan Y, Wu G, Tan F, Ding L.

Phase II trial of X-396 (ensartinib) for Chinese patients with ALK (+) non–small-cell lung cancer who progressed on crizotinib. J Thorac Oncol. 2017;12(11 suppl 2):S2398 [abstract P2.04-003].

Wu Y, Mok T, Reck M, Wakelee H, Liang C, Tan F, Harrow K, Oertel V, Dukart G, Ding L, Horn L.

First-line ensartinib (X396) versus crizotinib in advanced ALK-rearranged NSCLC (eXalt3): a randomized, open-label, phase 3 study. J Thorac Oncol. 2017;12(11 suppl 2):S2402 [abstract P2.04-012].

Wakelee H, Sanborn R, Nieva J, Waqar S, Brzezniak C, Bauman J, Neal J, Dukart G, Tan F, Harrow K, Liang C, Horn L.

Response to ensartinib in TKI naïve ALK+ NSCLC patients. J Thorac Oncol. 2017;12(11 suppl 2):S1826 [abstract MA 07.02].

2017 ASCO Annual Meeting
June 2-6, 2017; Chicago, IL

Horn L, Wu Y-L, Reck M, Liang C, Tan F, Harrow K, Oertel V, Dukart G, Mok T.

eXalt3: a phase III study of ensartinib (X-396) in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). J Clin Oncol. 2017;35(15 suppl) [abstract TPS8578].

IASLC 17th World Conference on Lung Cancer
December 4-7, 2016; Vienna, Austria

Horn L, Wakelee H, Reckamp K, Blumenschein G, Infante J, Carter C, Waqar S, Neal J, Gockerman J, Harrow K, Dukart G, Liang C, Gibbons J, Hernandez J, Newman-Eerkes T, Lim L, Lovly C.

Response and plasma genotyping from phase I/II trial of ensartinib (X-396) in patients (pts) with ALK+ NSCLC. J Thorac Oncol. 2017;12(1 suppl):S1159 [abstract P3.02a-001].

IASLC Chicago Multidisciplinary Symposium in Thoracic Oncology
September 22-24, 2016; Chicago, IL

Horn L, Wakelee H, Reckamp KL, Blumenschein G Jr, Infante JR, Carter CA, Waqar SN, Neal JW, Harrow K, Gockerman JP, Dukart G, Liang C, Gibbons JL, Hernandez J, Newman-Eerkes T, Lim L, Lovly CM.

Response and plasma genotyping from phase I/II trial of ensartinib (X-396) in patients (pts) with ALK+ NSCLC. J Thorac Oncol. 2016;11(11 suppl):S256-S257 [abstract MINI01.02].

IASLC 7th Latin American Conference on Lung Cancer
August 25-27, 2016; Panama City, Republic of Panama

Leal T, Wakelee H, Infante J, Blumenschein G, Reckamp K, Carter C, Waqar S, Gockerman J, Lovly C, Dukart G, Harrow K, Liang C, Gibbons J, Horn L.

Phase I/II trial of X-396, a novel ALK inhibitor, in patients with ALK+ NSCLC. J Thorac Oncol. 2016;11(10 suppl):S209-S210 [abstract P1.44; also presented as PD2.02].

2016 ASCO Annual Meeting
June 3-7, 2016; Chicago, IL

Horn L, Wakelee HA, Reckamp KL, Blumenschein GR, Infante JR, Carter CA, Waqar SN, Neal JW, Gockerman JP, Harrow K, Dukart G, Liang C, Gibbons JJ, Hernandez J, Newman-Eerkes T, Lim L, Lovly CM.

Plasma genotyping of patients enrolled on the expansion phase I/II trial of X-396 in patients (pts) with ALK+ non-small cell lung cancer (NSCLC). J Clin Oncol. 2016;34(15 suppl) [abstract 9056].