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ASCEND-7: Efficacy and Safety of Ceritinib Treatment in Patients with ALK-Positive Non-Small Cell Lung Cancer Metastatic to the Brain and/or Leptomeninges.

  • Chow, Laura Q M1
  • Barlesi, Fabrice2
  • Bertino, Erin M3
  • van den Bent, Martin J4
  • Wakelee, Heather A5
  • Wen, Patrick Y6
  • Chiu, Chao-Hua7
  • Orlov, Sergey8
  • Chiari, Rita9
  • Majem, Margarita10
  • McKeage, Mark11
  • Yu, Chong-Jen12
  • Garrido, Pilar13
  • Hurtado, Felipe K14
  • Arratia, Pilar Cazorla14
  • Song, Yuanbo14
  • Branle, Fabrice15
  • Shi, Michael14
  • Kim, Dong-Wan16
  • 1 University of Washington, Seattle, Washington and University of Texas at Austin, Dell Medical School, Department of Oncology, Austin, Texas.
  • 2 Aix-Marseille University, CNRS, INSERM, CRCM, APHM, Marseille, France. , (France)
  • 3 The Ohio State University Comprehensive Cancer Centre, Arthur G James Cancer Hospital and Richard J Solove Research Institute, Columbus, Ohio.
  • 4 Department of Neurology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands. , (Netherlands)
  • 5 Stanford University, Stanford, California.
  • 6 Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts.
  • 7 Department of Chest Medicine, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan. , (Taiwan)
  • 8 State Pavlov Medical University, St. Petersburg, Russia.
  • 9 Department of Oncology, AULSS6 Euganea, Padova, Italy. , (Italy)
  • 10 Hospital de La Santa Creu I Sant Pau, Barcelona, Spain. , (Spain)
  • 11 University of Auckland, Auckland, New Zealand. , (New Zealand)
  • 12 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. , (Taiwan)
  • 13 Department of Medical Oncology, Hospital Universitario Ramon Y Cajal, Madrid, Spain. , (Spain)
  • 14 Novartis Pharmaceuticals Corporation, East Hanover, New Jersey. , (Jersey)
  • 15 Novartis Pharma AG, Basel, Switzerland. , (Switzerland)
  • 16 Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea. , (North Korea)
Published Article
Clinical Cancer Research
American Association for Cancer Research
Publication Date
Jun 13, 2022
DOI: 10.1158/1078-0432.CCR-21-1838
PMID: 35091443


Central nervous system metastases are a prominent cause of morbidity and mortality in patients with ALK-positive (ALK+) non-small cell lung cancer (NSCLC). The phase II ASCEND-7 (NCT02336451) study was specifically designed to assess the efficacy and safety of the ALK inhibitor (ALKi) ceritinib in patients with ALK+ NSCLC metastatic to the brain and/or leptomeninges. Patients with active brain metastases were allocated to study arms 1 to 4 based on prior exposure to an ALKi and/or prior brain radiation (arm 1: prior radiotherapy/ALKi-pretreated; arm 2: no radiotherapy/ALKi-pretreated; arm 3: prior radiotherapy/ALKi-naïve; arm 4: no radiotherapy/ALKi-naïve). Arm 5 included patients with leptomeningeal carcinomatosis. Patients received ceritinib 750 mg once daily (fasted condition). Primary endpoint was investigator-assessed whole-body overall response rate (ORR) per RECIST v1.1. Secondary endpoints included disease control rate (DCR) and intracranial/extracranial responses. Per investigator assessment, in arms 1 (n = 42), 2 (n = 40), 3 (n = 12), and 4 (n = 44), respectively: whole-body ORRs [95% confidence interval (CI)] were 35.7% (21.6-52.0), 30.0% (16.6-46.5), 50.0% (21.1-78.9), and 59.1% (43.2-73.7); whole-body DCR (95% CI): 66.7% (50.5-80.4), 82.5% (67.2-92.7), 66.7% (34.9-90.1), and 70.5% (54.8-83.2); intracranial ORRs (95% CI): 39.3% (21.5-59.4), 27.6% (12.7-47.2), 28.6% (3.7-71.0), and 51.5% (33.5-69.2). In arm 5 (n = 18), whole-body ORR was 16.7% (95% CI, 3.6-41.4) and DCR was 66.7% (95% CI, 41.0-86.7). Paired cerebrospinal fluid and plasma sampling revealed that ceritinib penetrated the human blood-brain barrier. Ceritinib showed antitumor activity in patients with ALK+ NSCLC with active brain metastases and/or leptomeningeal disease, and could be considered in the management of intracranial disease. See related commentary by Murciano-Goroff et al., p. 2477. ©2022 American Association for Cancer Research.

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