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. Clinical cancer research : an official journal of the American Association for Cancer Research Chow, L. Q., Barlesi, F., Bertino, E. M., van den Bent, M. J., Wakelee, H. A., Wen, P. Y., Chiu, C., Orlov, S., Chiari, R., Majem, M., McKeage, M., Yu, C., Garrido, P., Hurtado, F. K., Cazorla Arratia, P., Song, Y., Branle, F., Shi, M., Kim, D. 1800


PURPOSE: Central nervous system (CNS) metastases are a prominent cause of morbidity and mortality in patients with ALK-positive (ALK+) non-small cell lung cancer (NSCLC). The phase 2 ASCEND-7 (NCT02336451) study was specifically designed to assess the efficacy and safety of ALK inhibitor (ALKi) ceritinib in patients with ALK+ NSCLC metastatic to the brain and/or leptomeninges.EXPERIMENTAL DESIGN: Patients with active brain metastases were allocated to study arms 1-4 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-naive; arm 4: no radiotherapy/ALKi-naive). 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.RESULTS: Per investigator assessment, in arms 1 (n=42), 2 (n=40), 3 (n=12), and 4 (n=44), respectively: whole-body ORRs (95% 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.CONCLUSIONS: 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.

View details for DOI 10.1158/1078-0432.CCR-21-1838

View details for PubMedID 35091443