88O - CNS activity of ensartinib in ALK+ non-small cell lung cancer (NSCLC) patients (pts)

Date 06 May 2017
Event ELCC 2017
Session Targeted therapies and management of brain metastasis
Presenter Karen Reckamp
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors K.L. Reckamp1, H.A. Wakelee2, S. Patel3, G. Blumenschein4, J.W. Neal2, B. Gitlitz5, S.N. Waqar6, F. Tan7, K. Harrow8, L. Horn9
  • 1City of Hope, 91010 - Duarte/US
  • 2Stanford Cancer Institute, Stanford/US
  • 3University of California, San Diego/US
  • 4Department Of Thoracic/head & Neck Medical Oncology, MD Anderson Cancer Center, Houston/US
  • 5University of Southern California Norris Comprehensive Cancer Center, Los Angeles/US
  • 6Washington University School of Medicine, 63110 - St Louis/US
  • 7Betta Pharmaceuticals, Beijing/CN
  • 8Xcovery Holding Company, 33408 - Palm Beach Gardens/US
  • 9Vanderbilt Ingram Cancer Center, Nashville, TN/US



Ensartinib (X-396) is a potent ALK small molecule TKI with additional activity against MET, ABL, Axl, EPHA2, LTK, ROS1 and SLK. In animal studies, CNS concentration of ensartinib in mice given at the therapeutic dose was 4 times higher than the IC50 for growth inhibition of ALK+ cells in vitro. Ensartinib was significantly more effective than crizotinib (C) at inhibiting the intracranial (IC) growth of the SH-SY5Y neuroblastoma model harboring the F1174L mutation. We subsequently evaluated the CNS activity of ensartinib in pts with ALK+ NSCLC.


In this multicenter phase I/II study, pts with ALK+ NSCLC were enrolled and given ensartinib orally on a continuous 28-day schedule. 225 mg QD was selected for further evaluation. Pts enrolled with asymptomatic CNS metastases (with or without systemic disease) who were ALK TKI naïve or had received prior C or a 2nd generation ALK TKI were allowed to enroll. Overall and systemic response was assessed using RECIST 1.1. CNS response was assessed using modified RANO criteria. Pts with only CNS disease had to have at least 1 measurable target lesion ≥ 3 mm in diameter.


26 pts with ALK+ NSCLC and baseline CNS metastases were treated at ≥ 200 mg. Of the 26 pts, 13 pts had baseline target lesions, and 13 pts had only non-target lesions. CNS responses were observed in ALK TKI naïve pts and pts that received prior C or a 2nd generation ALK TKI. In the 13 pts with baseline target CNS lesions, IC response rate (RR) was 69%, including 1 CR, and 31% had SD, a 100% disease control rate. In the 13 pts with only non-target baseline lesions, 1 CR was achieved and 8 pts had SD. The IC RR in the 3 ALK TKI naïve pts with baseline target lesions was 100%, and 62% in 8 pts that received prior C only. Of 2 pts with baseline target lesions who received a prior 2nd generation ALK TKI, 1 had a PR and 1 SD. Median duration of IC response in the 10 pts who responded (9 with target lesions, 1 with non-target lesions only) is 5.8+ months, with the longest duration being 24 months.


Our clinical findings support the preclinical results that the use of ensartinib may result in favorable therapeutic outcomes in pts with ALK+ NSCLC with CNS metastases. The ongoing phase III eXalt3 study will assess CNS RR and time to CNS progression in pts receiving 1st-line ensartinib vs C.

Clinical trial identification

NCT02767804 and NCT01625234

Legal entity responsible for the study

Xcovery Holding Company


Xcovery Holding Company


K. L. Reckamp: Xcovery Holding Company research funds to institution Ariad consultant and research funds to institution. H. A. Wakelee: Peregrin: Consultant/Independent contractor and honorarium recipient. Novartis: Grants/research support, consultant, honorarium recipient. ACEA: Consultant and honorarium recipient. Pfizer: Grants/research support, consultant, honorarium recipient. BMS: Grants/research support. Xcovery: Grants/research support. Celgene: Grants/research support. Roche/Genentech: Grants/research support. Medimmune: Grants/research support. Lilly: Grants/research support. S. Patel: Research funding from: Bristol-Myers Squibb, Eli Lilly, MedImmune, Pfizer, Roche/Genentech, Xcovery. Speaking fees from: Boehringer Ingelheim, Merck. G. Blumenschein: Grants/Research Support Recipient, Consultant- BMS, Bayer, Merck, Celgene Consultant- Clovis, AbbVie Grants/Research Support Recipient- Novartis, Xcovery, Astrazeneca. J. W. Neal: Consulting or Advisory role: Clovis Oncology, CARET/Physicians Resource Management, Nektar, Boehringer Ingelheim Research Funding- Genentech/Roche, Merck, ArQule, Novartis, Exelixis, Boehringer Ingelheim, Nektar. B. Gitlitz: Speakers Bureau for Lilly Speakers Bureau for Genentech. F. Tan: Manager- Xcovery Holding Company Chief Medical Officer- Betta Pharmaceuticals. K. Harrow: Xcovery Holding Company- Full-time Employee. L. Horn: Consulting for Xcovery Holding Company, BMS, BI, abbvie, Genentech, Merck. All other authors have declared no conflicts of interest.