445PD - ASCEND-6: single-arm, open label, multicenter phase 1/2 study of ceritinib in Chinese pts with advanced ALK-rearranged (ALK+) non-small cell lung c...

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Thoracic cancers
Topics Cytotoxic agents
Biomarkers
Non-Small-Cell Lung Cancer, Metastatic
Presenter Li Zhang
Citation Annals of Oncology (2016) 27 (suppl_9): ix139-ix156. 10.1093/annonc/mdw594
Authors L. Zhang1, Y. Shi2, D.S.W. Tan3, B. Hu4, L. Xiaoqing5, Y. Cheng6, J. Zhou7, T. An8, Y. Lu9, B. Zhu10, C. Bai11, A. Jappe12, V.Q. Passos13, Y.Y. Lau13, Q. Wang14, Y. Wu15
  • 1Medical Oncology, Sun Yat-Sen University Cancer Center, 510060 - Guangzhou/CN
  • 2Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100021 - Beijing/CN
  • 3Medical Oncology, National Cancer Center, 169610 - Singapore/SG
  • 4Clinical Pharmacology, Peking Union Medical College Hospital, 100032 - Beijing/CN
  • 5Pulmonary Oncology, 307 Hospital of the Academy of Military Medical Sciences, Cancer Center, 100071 - Beijing/CN
  • 6Thoracic Oncology, Jilin Province Cancer Hospital, 130012 - Changchun/CN
  • 7Respiratory And Thoracic Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003 - Hangzhou/CN
  • 8Thoracic Oncology, Beijing Cancer Hospital, 100048 - Beijing/CN
  • 9Thoracic Oncology, West China Hospital, Sichuan University, 610041 - Chengdu/CN
  • 10Oncology, Xinqiao Hospital, Third Military Medical University, 400037 - Chongqing/CN
  • 11Pulmonary Medicine, Shanghai Respiratory Research Institute, 200032 - Shanghai/CN
  • 12Oncology, Novartis Pharma AG, CH-4002 - Basel/CH
  • 13Oncology, Novartis Pharmaceutical Corporation, 07936 - East Hanover/US
  • 14Biometrics And Data Management, Beijing Novartis Pharma Co., Ltd, 100004 - Beijing/CN
  • 15Guangdong Lung Cancer Institute, Guangdong General Hospital, 510080 - Guangzhou/CN

Abstract

Background

In both ASCEND-1 and ASCEND-2 studies, ceritinib demonstrated durable responses and promising PFS in pts with ALK+ NSCLC pre-treated with chemotherapy and crizotinib. ASCEND-6 (NCT02040870) evaluated pharmacokinetics (PK), safety and efficacy of ceritinib in Chinese pts with ALK+ NSCLC who had progressive disease during or after crizotinib (irrespective of prior chemo [≤2]).

Methods

A total of 103 pts were enrolled, of which, 20 pts completed 5-day PK run-in period (phase I; single dose of ceritinib 750mg [fasted]) followed by 120 hrs of PK sampling before starting continuous daily dosing; all other pts started on continuous daily dosing ceritinib 750mg fasted (28 day cycles). Primary endpoint: PK, safety and tolerability. Key secondary endpoint: investigator-assessed ORR and other secondary endpoints: DOR, DCR, OIRR and PFS per RECIST 1.1. Data cut off: 30 Oct 2015.

Results

Of 103 pts: median age (range) was 49 (26–76) yrs; 53.4% were male; 92.2% had WHO PS ≤ 1; 69.9% pts received ≥1 line of prior chemo; 63.1% had brain metastases at baseline; and crizotinib was the last treatment before enrollment for all pts. Median duration of exposure and follow-up time were 7.06 (0–18.8) and 8.3 (0.1–18.6) mos, respectively. Median Tmax (n = 16) was ∼ 6 hrs; Geometric means of AUC0-24h (n = 16) and Cmax (n = 16) at steady-state were 22000 ng*h/mL, and 1080 ng/mL, respectively.rn

Table: 445PD

rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn
Whole-body responseInvestigator N = 103
ORR (CR+PR), n (%) [95% CI]42 (40.8) [31.2, 50.9]
DCR (CR+PR+SD+non-CR/non-PD), n (%) [95% CI]80 (77.7) [68.4, 85.3]
Median DOR, Mos [95% CI] 9-months event-free probability, DOR, [95% CI]8.5 [7.3, NE] 47.0 (28.5, 63.5)
Median PFS, Mos [95% CI]5.7 [5.4, 7.5]
Intracranial responses in patients with measurable diseasen = 23
Overall intracranial response (CR+PR), n (%) [95% CI]9 (39.1) [19.7,61.5]
Intracranial DCR (CR+PR+SD+non-CR/non-PD), n (%) [95% CI]19 (82.6) [61.2, 95.0]
rn

Most common AEs regardless of study drug relationship (mostly grade 1/2): diarrhea (72.8%) vomiting (61.2%), increased ALT (58.3%), increased AST (57.3%), and nausea (55.3%). AEs leading to discontinuation reported in 12.6%.

rn

Conclusions

PK profile of ceritinib in Chinese pts was comparable to multinational phase 1 study (ASCEND-1). Consistent with ASCEND-1 and ASCEND-2 studies, ceritinib demonstrated clinical activity and manageable safety in Chinese pts with ALK+ NSCLC having previously treated with chemotherapy and crizotinib.

Clinical trial indentification

NCT02040870

Legal entity responsible for the study

Novartis Pharmaceutical Corporation

Funding

Novartis Pharmaceutical Corporation

Disclosure

L. Zhang: Consulting/advisory: AstraZeneca, Boehringer ingelheim, Roche Research funding fees: Pfizer, BMS, Lilly. D.S.W. Tan: Consulting/advisory: Novartis, Bayer, Boehringer Ingelheim, Eisai, Loxo Oncology, Celgene, Merrimack, Pfizer Honoraria: Novartis, Pfizer Research funding fees: Novartis, Bayer, GlaxoSmithKline, AstraZeneca. A. Jappe, Q. Wang: Employee: Novartis. V.Q. Passos, Y.Y. Lau: Employee and stocks: Novartis. Y-L. Wu: Honoraria: AstraZeneca, Roche, Eli Lilly, Pfizer, Sanofi. All other authors have declared no conflicts of interest.