Author of

• 18374

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  P3.02b - Poster Session with Presenters Present (ID 494)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 18440

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    P3.02b-066 - Phase II Trial of the C-Met Inhibitor Tepotinib in Advanced Lung Adenocarcinoma with MET Exon 14 Skipping Mutations after Failure of Prior Therapy (ID 5626)

    14:30 - 14:30  |  Author(s): U. Stammberger
    • Abstract

    Background:
    Background: The MET proto-oncogene is activated in 3-4% of lung adenocarcinomas through mutations that lead to aberrant mRNA splicing and skipping of exon 14, which encodes a region of the c-Met protein that regulates its degradation. c-Met lacking exon 14 accumulates as a functional receptor on the cell surface and appears to act as a true oncogenic driver, exclusive of other known oncogenic drivers such as EGFR and ALK. Emerging data suggest that lung adenocarcinomas harboring MET with exon 14-skipping mutations are sensitive to c-Met kinase inhibitors. The highly selective and potent c-Met inhibitor tepotinib has been shown to be well tolerated and active in several phase I/Ib trials, with activity appearing greatest in c-Met-positive tumors. The recommended dose has been established as 500 mg/day. This open-label phase II trial (EudraCT 2015-005696-24) is investigating the efficacy of tepotinib in patients with lung adenocarcinoma harboring MET mutations that cause exon 14 skipping.
    
    Methods:
    Trial design: Eligible patients are adults with histologically confirmed stage IIIB/IV lung adenocarcinoma who have failed at least one line of systemic therapy, including a platinum doublet-containing regimen, but have failed no more than two active therapies. Tumors cannot harbor EGFR mutations that confer sensitivity to EGFR TKIs, or ALK rearrangements, but must exhibit MET mutations that are known to lead to exon 14 skipping, confirmed by a central laboratory. The primary objective is to assess the efficacy of tepotinib according to confirmed objective response as per independent review determined by RECIST v1.1. Secondary objectives include further assessment of efficacy, and assessment of safety, pharmacokinetics, and quality of life. Patients receive tepotinib 500 mg/day in 21 day cycles until disease progression, intolerable toxicity, or withdrawal from treatment for other reasons. Recruitment of 60 patients in Europe, USA, and Japan is planned. This trial will establish the activity, safety, and tolerability of tepotinib in patients with lung adenocarcinoma harboring c-Met exon 14 alterations.
    
    Results:
    section not applicable
    
    Conclusion:
    section not applicable