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Miguel F Miranda

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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-80 - ELIOS: A Multicenter, Open-Label, Molecular Profiling Study of Patients with EGFRm and NSCLC Treated with Osimertinib (ID 13198)

      16:45 - 18:00  |  Author(s): Miguel F Miranda

      • Abstract
      • Slides


      Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard-of-care for locally advanced/metastatic non-small cell lung cancer (NSCLC) harbouring EGFR sensitizing mutations (EGFRm). Osimertinib, a third-generation, CNS-active EGFR-TKI potently and selectively inhibits both L858R and exon19del sensitizing EGFRm and T790M mutations, is now approved for first-line treatment of EGFRm-NSCLC. Studies of osimertinib resistance have focused on patients previously treated with first-/second-generation EGFR-TKIs; however, resistance mechanisms to first-line osimertinib are not well-described.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      ELIOS (NCT03239340) is a phase 2, open-label, single-arm study designed to prospectively characterize the molecular profile of patients who progress on first-line osimertinib. The study will enroll patients (n=100) with locally advanced/metastatic non-squamous EGFRm-NSCLC nonamenable to curative surgery/chemoradiation, WHO performance status 0-1, and life expectancy ≥12 weeks. Patients must have EGFRm known to be associated with EGFR-TKI sensitivity, must be EGFR-TKI treatment-naïve, and be eligible to receive first-line osimertinib therapy. Patients with clinically significant toxicities, history of interstitial lung disease, and EGFR exon 20 insertion will be excluded. All patients will receive 80 mg osimertinib orally once daily and will continue treatment beyond progression if they show continued clinical benefit. Mandatory tumor biopsies will be obtained prior to treatment initiation and following investigator-assessed disease progression. An optional biopsy may be obtained following 2-3 weeks of treatment. Longitudinal plasma samples will be collected for plasma-derived circulating tumor DNA (ctDNA) analysis. Tumor- and plasma-derived specimens will be analyzed by next-generation sequencing; additional exploratory analyses are also planned. The primary endpoint is the proportion of patients with a given genetic/proteomic marker at disease progression (investigator-assessed, RECIST v1.1). Relevant genetic and proteomic markers will be selected based on the profile comparison at disease progression to baseline. Relevant markers of resistance to first-line osimertinib may include, but are not limited to, EGFR resistance mutations (including C797S) and cMET/HER2 amplification; this analysis may reveal other, potentially novel, resistance mechanisms. Secondary endpoints include progression-free survival, objective response rate, duration of response, disease control rate, assessment of osimertinib efficacy post-progression using time to treatment discontinuation, and time to first subsequent therapy. Efficacy analyses based on predefined subgroups (according to the patient molecular profiles) including presence of baseline T790M mutation, EGFR Ex19del or L858R mutations, and EGFR Ex19del or L858R detectable in ctDNA, will be assessed. Safety will also be assessed. Primary analysis will be performed when ≥50 patients have paired biopsies upon progression. Recruitment is in process (May 1, 2018).

      4c3880bb027f159e801041b1021e88e8 Result

      Section not applicable

      8eea62084ca7e541d918e823422bd82e Conclusion

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