Ceritinib plus Nivolumab in Patients with Advanced ALK-Rearranged Non-Small Cell Lung Cancer: Results of an Open-Label, Multicenter, Phase 1B Study. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

Enriqueta Felip, Filippo G. de Braud, Michela Maur, Herbert H. Loong, Alice Tsang Shaw, Johan F. Vansteenkiste, Thomas John, Geoffrey Liu, Martijn P. Lolkema, Giovanni Selvaggi, Vanessa Giannone, Pilar Cazorla, Jason Baum, O. Alejandro Balbin, Luojun Victor Wang, Yvonne Y. Lau, Jeffrey W. Scott, Daniel Shao-Weng Tan

Research output: Contribution to journalArticlepeer-review

Abstract

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Original languageEnglish
Pages (from-to)392-403
Number of pages12
JournalJournal of Thoracic Oncology
Volume15
Issue number3
DOIs
Publication statusPublished - 2020

Keywords

  • Humans
  • Nivolumab
  • *NSCLC
  • *Nivolumab
  • *PD-1
  • *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics
  • *Lung Neoplasms/drug therapy/genetics
  • *ALK
  • *Ceritinib
  • Anaplastic Lymphoma Kinase/genetics
  • Pyrimidines
  • Sulfones

Fingerprint

Dive into the research topics of 'Ceritinib plus Nivolumab in Patients with Advanced ALK-Rearranged Non-Small Cell Lung Cancer: Results of an Open-Label, Multicenter, Phase 1B Study. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer'. Together they form a unique fingerprint.

Cite this