Ceritinib in advanced anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC): Results of the ASCEND-1 trial.

Lung Cancer - Non-Small Cell Metastatic
Session Type and Session Title: 
Oral Abstract Session, Lung Cancer - Non-small Cell Metastatic
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 8003^)
Dong-Wan Kim, Ranee Mehra, Daniel Shao-Weng Tan, Enriqueta Felip, Laura Quan Man Chow, D. Ross Camidge, Johan F. Vansteenkiste, Sunil Sharma, Tommaso De Pas, Gregory J. Riely, Benjamin J. Solomon, Juergen Wolf, Michael Thomas, Martin H. Schuler, Geoffrey Liu, Armando Santoro, Margarida Geraldes, Anthony Boral, Alejandro Javier Yovine, Alice Tsang Shaw; Seoul National University Hospital, Seoul, South Korea; Fox Chase Cancer Center, Philadelphia, PA; National Cancer Centre, Singapore, Singapore; Vall d'Hebron University Hospital, Barcelona, Spain; University of Washington, Seattle, WA; University of Colorado Cancer Center, Aurora, CO; University Hospital KU Leuven, Leuven, Belgium; University of Utah Huntsman Cancer Institute, Salt Lake City, UT; Instituto Europeo di Oncologia, Milan, Italy; Memorial Sloan Kettering Cancer Center, New York City, NY; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; University Hospital Cologne, Cologne, Germany; Thoraxklinik, University of Heidelberg, Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research, Heidelberg, Germany; University Hospital Essen, University Duisburg-Essen, Essen, Germany and German Cancer Consortium, Heidelberg, Germany; Ontario Cancer Institute, Princess Margaret Cancer Centre, Toronto, ON, Canada; IRCCS Institute Clinico Humanitas, Milan, Italy; Novartis Pharma, East Hanover, NJ; Novartis Institutes for BioMedical Research, Cambridge, MA; Novartis Pharma AG, Basel, Switzerland; Massachusetts General Hospital, Boston, MA

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: ALK+ NSCLC is sensitive to crizotinib (CRZ) but patients (pts) invariably progress. Ceritinib (LDK378) is a novel ALK inhibitor (ALKi) more potent than CRZ in enzymatic and cell-based assays and CRZ-resistant animal models. Prior results from this Phase I study (ASCEND-1) established a MTD of 750 mg/d. Methods: Adult pts with advanced ALK+ cancers received oral ceritinib q.d. After MTD determination, pts were enrolled to expansion groups: ALKi pretreated (PT) NSCLC; ALKi naive NSCLC; non-NSCLC diseases. Results are reported for all NSCLC pts receiving ceritinib at the recommended dose (750 mg/d). Results: 255 pts from 11 countries were treated at 750 mg/d. 246 pts had ALK+ NSCLC, with 4.5 months’ median follow-up; of these, 67% had received ≥2 anticancer therapies; ORR was ≥60% in each subgroup of pts with 0, 1, 2, and 3 prior anticancer regimens. 83 pts were ALKi naïve. All 163 ALKi PT pts had received CRZ – 78% as their last prior therapy – and 92% had progressive disease on prior ALKi. Investigator efficacy assessments are presented for 180 NSCLC pts who received first dose of ceritinib ≥18 wks prior to cut-off (2 Aug 2013). Of all 255 pts, the most common AEs were diarrhea (84%), nausea (77%), vomiting (57%), fatigue (36%), and ALT increased (36%). The most common Grade 3/4 AEs were ALT increased (21%), and AST increased (8%). Ceritinib treatment is ongoing for 58% of pts. During the dosing period dose reductions occurred in 133 pts (52.2%), all due to an AE. Only 24 (9.4%) pts discontinued ceritinib due to an AE. Conclusions: Ceritinib 750 mg/d has rapid, durable and high antitumor activity in ALK+ NSCLC pts, regardless of prior treatment with ALKi, providing effective treatment in this pt population. Clinical trial information: NCT01283516.

Endpoint ALKi PT
ALK naive
ORR, n (%) [95% CI] 67 (55.4%)
[46.1, 64.4]
41 (69.5%)
[56.1, 80.8]
108 (60.0%)
[52.4, 67.2]
DOR (Median [95% CI]) 7.4 mos
[5.4, 10.1]
[5.6, NE]
9.7 mos
[6.9, 11.4]
Time to first response
(Median [min, max])
6.1 wks
[4.6, 24.1]
6.1 wks
[3.0, 24.1]
6.1 wks
[3.0, 24.1]
PFS (Median [95% CI]) 6.9 mos
[5.4, 8.7]
[6.7, NE]
7.0 mos
[6.2, 10.1]

Abbreviation: NE, not estimable. a DOR rate at 12 mos: 71.1% (95% CI: 49.8, 84.6). b PFS rate at 12 mos: 58.1% (95% CI: 41.6, 71.5).