Please use this identifier to cite or link to this item:
Title: Ceritinib plus Nivolumab in Patients with Advanced ALK-Rearranged Non-Small Cell Lung Cancer: Results of an Open-Label, Multicenter, Phase 1B Study.
Austin Authors: Felip, Enriqueta;de Braud, Filippo G;Maur, Michela;Loong, Herbert H;Shaw, Alice Tsang;Vansteenkiste, Johan F;John, Thomas ;Liu, Geoffrey;Lolkema, Martijn P;Selvaggi, Giovanni;Giannone, Vanessa;Cazorla, Pilar;Baum, Jason;Balbin, O Alejandro;Wang, Luojun Victor;Lau, Yvonne Y;Scott, Jeffrey W;Tan, Daniel Shao-Weng
Affiliation: Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona, Spain.
University of Milan, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
AOU Policlinico of Modena, University of Modena and Reggio Emilia, Modena, Italy
The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
Massachusetts General Hospital, Boston, Massachusetts
University Hospital KU Leuven, Leuven, Belgium
Princess Margaret Cancer Centre, Toronto, Ontario, Canada
Erasmus MC Cancer Institute, Rotterdam, The Netherlands
Bristol-Myers Squibb, Princeton, New Jersey
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey
Novartis Institutes for Biomedical Research, Cambridge, Massachusetts
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey
National Cancer Centre Singapore, Singapore
Austin Health
Issue Date: Mar-2020
Date: 2019-10-18
Publication information: Journal of Thoracic Oncology 2020; 15(3): 392-403
Abstract: Induction of programmed death ligand 1 (PD-L1) expression due to constitutive oncogenic signaling has been reported in NSCLC models harboring echinoderm microtubule associated protein like 4 gene (EML4)-ALK receptor tyrosine kinase gene (ALK) rearrangements. We assessed the safety and activity of ceritinib plus nivolumab in these patients. In this open-label, phase 1B, multicenter, dose escalation and expansion study, previously treated (with ALK receptor tyrosine kinase [ALK] inhibitor [ALKI]/chemotherapy) or treatment-naive patients with stage IIIB or IV ALK-rearranged NSCLC received nivolumab, 3 mg/kg intravenously every 2 weeks, plus ceritinib, 450 mg/300 mg daily, with a low-fat meal. In total, 36 patients were treated (a 450-mg cohort [n=14] and a 300-mg cohort [n=22]). In the 450-mg cohort, four patients experienced dose-limiting toxicities. In the 300-mg cohort, two patients experienced dose-limiting toxicities. Among ALKI-naive patients, the overall response rate (ORR) was 83% (95% confidence interval [CI]: 35.9-99.6) in the 450-mg cohort and 60% (95% CI: 26.2-87.8) in the 300-mg cohort. Among ALKI-pretreated patients, the ORR was 50% (95% CI: 15.7-84.3) in the 450-mg cohort and 25% (95% CI: 5.5-57.2) in the 300-mg cohort. The ORR point estimate was observed to be greater in patients who were positive for PD-L1 than in those who were negative for PD-L1, with overlapping CIs (e.g., at a cutoff ≥1% PD-L1, 64% of patients [95% CI: 35.1-87.2] had confirmed responses as compared with those with negative PD-L1 staining (31% [95% CI: 11.0-58.7]). The most frequently reported grade 3 or 4 adverse events were increased alanine aminotransferase level (25%), increased gamma-glutamyl transferase level (22%), increased amylase level (14%), increased lipase level (11%), and maculopapular rash (11%). The incidence of all-grade rash (grouped term) was 64% in both cohorts; grade 3 rash was reported in 29% and 14% of patients in the 450-mg and 300-mg cohorts, respectively; no grade 4 rash was reported. Ceritinib plus nivolumab has activity; ORR appears to correlate with PD-L1 at baseline. Toxicity, especially rash, is more common than with either single agent.
DOI: 10.1016/j.jtho.2019.10.006
Journal: Journal of Thoracic Oncology
PubMed URL: 31634667
Type: Journal Article
Subjects: ALK
Appears in Collections:Journal articles

Show full item record

Page view(s)

checked on Sep 29, 2023

Google ScholarTM


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.