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Title: Ceritinib plus nivolumab in patients with advanced ALK-rearranged non-small-cell lung cancer: results of an open-label, multicenter, phase 1B study: Ceritinib plus nivolumab in ALK-rearranged NSCLC.
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;Shao-Weng Tan, Daniel
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
A.O. U Policlinico of Modena, University of Modena e R. Emilia, Italy
The Chinese University of Hong Kong, Hong Kong SAR, China
Massachusetts General Hospital, Boston, MA, USA
University Hospital KU Leuven, Leuven, Belgium
Princess Margaret Cancer Centre, Toronto, ON, Canada
Erasmus MC Cancer Institute Rotterdam, The Netherlands
Bristol-Myers Squibb, Princeton, NJ, USA
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
Novartis Institutes for Biomedical Research, Cambridge, MA, USA
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
National Cancer Centre Singapore, Singapore
Austin Health, Heidelberg, Victoria, Australia
Issue Date: 18-Oct-2019 2019-10-18
Publication information: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 2019; online first: 18 October
Abstract: Induction of PD-L1 expression due to constitutive oncogenic signaling has been reported in NSCLC models harboring EML4-ALK rearrangements. We assessed safety and activity of ceritinib plus nivolumab in these patients. In this open-label, phase 1B, multicenter, dose-escalation and expansion study, previously treated (ALK inhibitor [ALKi]/chemotherapy) or treatment-naïve patients with stage IIIB/IV ALK-rearranged NSCLC received nivolumab 3 mg/kg intravenously every 2 weeks plus ceritinib (450 mg/300 mg) daily with low-fat meal. In total, 36 patients were treated (450 mg cohort [n=14]; 300 mg cohort [n=22]). In the 450 mg cohort, four patients experienced DLTs. In the 300 mg cohort, two patients experienced DLTs. Among ALKi-naïve patients, the overall response rate (ORR) was 83% (95% 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% (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 as compared to those who were negative for PD-L1 with overlapping CIs (e.g., at a cutoff ≥1% PD-L1, 64% [95% CI 35.1-87.2] patients had confirmed responses as compared to those with negative PD-L1 staining (31% [95% CI 11.0-58.7]). Most frequently reported grade 3/4 adverse events were increased alanine aminotransferase (ALT) (25%), increased gamma-glutamyl transferase (22%), increased amylase (14%), increased lipase (11%), and maculopapular rash (11%). Incidence of all grade rash (grouped term) was 64% in both cohorts; grade 3 rash was reported in 29% and 14% 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
PubMed URL: 31634667
Type: Journal Article
Subjects: ALK
Appears in Collections:Journal articles

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