Protocol Design for the Bench to Bed Trial in Alectinib-Refractory Non–Small-Cell Lung Cancer Patients Harboring the EML4-ALK Fusion Gene (ALRIGHT/OLCSG1405)

Hideko Isozaki, Katsuyuki Hotta, Eiki Ichihara, Nagio Takigawa, Kadoaki Ohashi, Toshio Kubo, Takashi Ninomiya, Kiichiro Ninomiya, Naohiro Oda, Hiroshige Yoshioka, Hirohisa Ichikawa, Masaaki Inoue, Ichiro Takata, Takuo Shibayama, Shoichi Kuyama, Keisuke Sugimoto, Daijiro Harada, Shingo Harita, Toshiaki Sendo, Mitsune TanimotoKatsuyuki Kiura

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Based on our preclinical study results, which showed that the activation of the hepatocyte growth factor/MET pathway is a potential mechanism of acquired resistance to alectinib, we launched the ALRIGHT (OLCSG1405 [alectinib-refractory non–small-cell lung cancer patients harboring the EML4-ALK fusion gene]), a phase II trial of the anaplastic lymphoma kinase (ALK)/MET inhibitor crizotinib in patients with non–small-cell lung cancer refractory to alectinib and harboring the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene. Patients with ALK-rearranged tumors who have developed disease progression during alectinib treatment will receive crizotinib monotherapy until disease progression or the occurrence of unacceptable toxicity. The primary endpoint is set as the objective response rate, assuming that a response in 50% of eligible patients will indicate potential usefulness and that 15% would be the lower limit of interest (1-sided α of 0.05, β of 0.20). The estimated accrual number of patients is 9. The secondary endpoints include progression-free survival, overall survival, adverse events, and patient-reported outcomes. We will also take tissue samples before crizotinib monotherapy to conduct an exploratory analysis of ALK and hepatocyte growth factor/MET expression levels and gene alterations (eg, mutations, amplifications, and translocations). We will obtain information regarding whether crizotinib, which targets not only ALK, but also MET, can truly produce efficacy with acceptable safety profiles in ALK+ non–small-cell lung cancer even in the alectinib-refractory setting.

Original languageEnglish
Pages (from-to)602-605
Number of pages4
JournalClinical Lung Cancer
Volume17
Issue number6
DOIs
Publication statusPublished - Nov 1 2016

Keywords

  • ALK inhibitor
  • Crizotinib
  • EML4-ALK
  • Lung carcinoma
  • MET

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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