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J. McGill



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    P3.04 - Clinical Design, Statistics and Clinical Trials (ID 720)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Clinical Design, Statistics and Clinical Trials
    • Presentations: 1
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      P3.04-012 - Phase 1 Study of the AXL Inhibitor DS-1205c in Combination with Osimertinib in Subjects with Metastatic or Unresectable EGFR-Mutant NSCLC (ID 10172)

      09:30 - 09:30  |  Author(s): J. McGill

      • Abstract
      • Slides

      Background:
      In patients with metastatic EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC), resistance to EGFR tyrosine kinase inhibition arises from the T790M EGFR mutation in over half of cases; up-regulation of “bypass track” activity in non-EGFR signaling pathways is observed in other cases. Up-regulation of expression of the AXL tyrosine kinase has been observed in EGFRm NSCLC patients experiencing disease progression on erlotinib, and xenograft studies have explored the role of AXL inhibition in combination with EGFR TKI treatment in overcoming such resistance. DS-1205c is a novel, orally administered, specific small molecule inhibitor of AXL.

      Method:
      Trial Design: This is a multicenter, open-label, Phase 1 study of DS-1205c in combination with osimertinib in metastatic or unresectable EGFR-mutant NSCLC subjects experiencing disease progression during treatment with erlotinib, gefitinib, or afatinib, and without T790M resistance mutation. Eligible subjects are at least 18 years of age, have ECOG PS 0 or 1, have radiological documentation of disease progression while receiving continuous treatment with erlotinib, gefitinib, or afatinib, have at least one measurable lesion per RECIST v1.1, do not have spinal cord compression or clinically active brain metastases, and do not have any factors that increase the risk of QTc prolongation. This study includes two parts: Dose Escalation and Dose Expansion. In Dose Escalation, subjects receive DS-1205c during a run-in period, followed by continuous combination treatment with DS-1205c and osimertinib. Escalation of DS-1205c dosing between subjects is determined from dose-limiting toxicity data in subjects, guided by the modified Continuous Reassessment Method (mCRM) using a Bayesian logistic regression model (BLRM) following the escalation with overdose control (EWOC) principle. In Dose Expansion, subjects receive DS-1205c at the recommended dose for expansion determined in Dose Escalation, in combination with osimertinib. Primary objectives are to determine the safety, tolerability, and recommended dose for expansion of DS-1205c in combination with osimertinib. Secondary objectives are to assess the pharmacokinetic parameters of DS-1205a (free form of DS-1205c), osimertinib, and osimertinib active metabolites, and to assess antitumor activity (RECIST v1.1).Clinicaltrials.gov identifier: NCT03255083

      Result:
      Section not applicable

      Conclusion:
      Section not applicable

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