141PD - Whole body and intracranial efficacy of ceritinib in patients (pts) with crizotinib (CRZ) pretreated, ALK-rearranged (ALK+) non-small cell lung can...

Date 14 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Targeting EGFR and ALK driven tumours
Topics Anticancer agents
Non-Small Cell Lung Cancer
Therapy
Biological Therapy
Presenter Enriqueta Felip
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors E. Felip1, L. Crinò2, D. Kim3, D.R. Spigel4, M. Nishio5, T.S.K. Mok6, G. Scagliotti7, D. Cesic8, S. Sutradhar9, A.T. Shaw10
  • 1Medical Oncology Service, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 2Oncologia Medica, Ospedale S. Maria della Misericordia, 06156 - Perugia/IT
  • 3Department Of Internal Medicine, Seoul National University Hospital, 110-744 - Seoul/KR
  • 4Medical Oncology, Sarah Cannon Research Institute, Nashville/US
  • 5Thoracic Medical Oncology, Cancer Institute Hospital of JFCR, 135-8550 - Tokyo/JP
  • 6Dept. Of Clinical Oncology, Chinese University of Hong Kong Prince of Wales Hospital, Hong Kong/CN
  • 7Oncology, University of Turino, 10043 - Torino/IT
  • 8Gma Oncology, Novartis Pharmaceuticals Corporation, 07936-1080 - East Hanover/US
  • 9Gma Biostatistics, Novartis Pharmaceuticals Corporation, 07936-1080 - East Hanover/US
  • 10Cancer Center, Massachusetts General Hospital, 02114 - Boston/US

Abstract

Background

BM are a common site of disease progression in pts with ALK+ NSCLC, including those who have received CRZ. Ceritinib is a selective oral ALK inhibitor with a 20-fold greater potency than CRZ in vitro. Here we present efficacy outcomes in pts with CRZ pretreated ALK+ NSCLC and baseline BM, treated with ceritinib in the ASCEND-1 (phase 1) and ASCEND-2 (phase 2) trials.

Methods

In both trials, pts with CRZ pretreated, ALK+ NSCLC and clinically / neurologically stable baseline BM received oral ceritinib 750 mg/day; the majority of pts had also received chemotherapy. CT/MRI scans were performed in pts at baseline and every 6 (ASCEND-1) or 8 (ASCEND-2) weeks thereafter. Efficacy analyses (by Blinded Independent Review Committee [BIRC]) assessed whole body responses according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 and 1.1 criteria for ASCEND-1 and ASCEND-2, respectively. Pooled intracranial responses, by BIRC, were evaluated (retrospectively in ASCEND-1; prospectively in ASCEND-2) in pts with measureable BM at baseline according to RECIST 1.1 criteria. 141PDT1 Table 1.

 ASCEND-1ASCEND-2 
Data cut-off14 Apr 201413 Aug 2014 
Number of patients with BM at baseline98100 
Duration of follow-up, months (range)9.8 (0.1–22.2)11.2 (0.2–18.9) 
Whole body response per BIRC 
Overall response rate, % [95% CI]41.8 [31.9, 52.2]32.0 [23.0, 42.1] 
Disease control rate, % [95% CI]69.4 [59.3, 78.3]64.0 [53.8, 73.4] 
Median duration of responsea, months [95% CI]8.2 [5.6, 13.1]9.3 [5.5, 12.9] 
Median progression-free survival, months [95% CI]6.7 [5.4, 9.5]6.8 [5.4, 7.4] 
Intracranial response per BIRCPooled
Number of patients with measurable BM at baseline283361
Overall intracranial response rate, % [95% CI]35.7 [18.6, 55.9]39.4 [22.9, 57.9]37.7 [25.6, 51.0]
Intracranial disease control rate, % [95% CI]60.7 [40.6, 78.5]84.8 [68.1, 94.9]73.8 [60.9, 84.2]
Median intracranial duration of responsea, months [95% CI]11.1 [2.8, NE]12.8 [4.0, 13.2]12.8 [6.9, NE]
NE, non-evaluable.a Duration of response calculated for patients with confirmed complete or partial response CI, confidence interval.

Results

Of the 98 and 100 CRZ pretreated pts with baseline BM enrolled in the ASCEND-1 and ASCEND-2 trials, respectively, 69.4% and 72.0% had received prior radiotherapy to the brain. Ceritinib showed efficacy in the whole body and in brain metastases (Table 1). Tolerability was acceptable. The most common AEs (any grade, regardless of study drug relationship) were (ASCEND-1; ASCEND-2) nausea (83.7%; 82.0%), diarrhea (76.5%; 82.0%) and vomiting (60.2%; 64.0%); 10 and 7 pts discontinued due to AEs from ASCEND-1 and ASCEND-2, respectively.

Conclusions

Ceritinib treatment resulted in clinically meaningful whole body and intracranial activity with an acceptable tolerability profile in pts with CRZ pretreated, ALK+ NSCLC and baseline BM.

Clinical trial identification

NCT01283516 (ASCEND-1); NCT01685060 (ASCEND-2)

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation

Funding

Novartis Pharmaceuticals Corporation

Disclosure

E. Felip: Consultancy fees from Boehringer Ingelheim, Eli Lilly, Pfizer, Roche, BMS, MSD, Novartis; Board/Advisory Committee Member for MSD, Novartis, Roche; Speaker for Boehringer Ingelheim, Eli Lilly, Pfizer, Roche, BMS, MSD, Novartis. L. Crinò: Honoraria for scientific talks from Pfizer, Bristol, Novartis, Boheringer. D.R. Spigel: previously acted in a consulting or advisory role for Novartis, Roche/Genentech and Ariad. M. Nishio: Consulting/Speaker bureau/Research: AZ, BMS, Chugai Pharma, Daiichi Sankyo Healthcare, Elekta, Lily, Nichirei Biosciences, Novartis, Ono Pharma, Pfizer, Sanofi, Taiho Pharma, Takeda Pharma. T. Mok: Consulting/Honoraria/Speakers bureau: AZ, Roche/Genentech, Pfizer, Eli Lilly, BI, Merck Serono, MSD, Janssen, Clovis Oncology, BioMarin, GSK, Novartis, SFJ Pharma, ACEA Biosciences, Vertex Pharma, BMS, AVEO & Biodesix, Prime Oncology, Amgen. G. Scagliotti: Honoraria and Consulting/advisory: Eli Lilly, Astra Zeneca, Pfizer, Roche, Clovis Speaker bureau: Eli Lilly. D. Cesic, S. Sutradhar: Employee of Novartis Pharma. A.T. Shaw: Grants and personal fees from Novartis; personal fees from Ignyta, Blueprint, Pfizer, Ariad, Genentech, Roche, EMD Serono, Daiichi-sankyo and Taiho. All other authors have declared no conflicts of interest.