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Juliann Chmielecki



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    P2.01 - Advanced NSCLC (ID 159)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.01-22 - ORCHARD: A Phase II Platform Study in Patients with Advanced NSCLC Who Have Progressed on First-Line Osimertinib Therapy (ID 1303)

      10:15 - 18:15  |  Author(s): Juliann Chmielecki

      • Abstract
      • Slides

      Background

      Osimertinib is a third-generation, central nervous system (CNS)-active, irreversible epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR-TKI sensitising mutations (EGFRm) and EGFR T790M. First-line osimertinib has demonstrated superiority in progression-free survival (PFS) compared with first-generation EGFR-TKIs in patients with EGFRm advanced NSCLC (Soria et al, NEJM 2018). The most common resistance mechanisms to first-line osimertinib identified from plasma samples are MET amplification (15%) and EGFR C797S (7%) (Ramalingam et al, Ann Oncol 2018). Further clinical studies are needed to better understand resistance mechanisms and evaluate post-progression targeted treatment options.

      Method

      ORCHARD is an open-label, multicentre, biomarker-directed, Phase II platform study evaluating the optimal treatment for individual patients with EGFRm NSCLC depending on their underlying resistance mechanism to first-line osimertinib.

      Adult patients with EGFRm locally advanced/metastatic NSCLC and radiological progression on first-line osimertinib monotherapy will be eligible.

      Treatment assignment will be based on molecular characterisation of the tumour at progression from a mandatory tissue biopsy.

      ORCHARD will comprise of three groups assigned by tumour molecular profile (Figure). An adaptive design allows addition of new treatments based on emerging findings. Tumour assessments (RECIST 1.1) will be performed every 6 weeks for the first 24 weeks and every 9 weeks thereafter until progression. An interim analysis of each cohort will be performed when ≈16 patients have reached the second on-treatment RECIST assessment. Based on preliminary signals, the cohort may be stopped or expanded to 30–40 patients for further evaluation.

      The primary outcome is investigator-assessed objective response rate; secondary outcomes include PFS, duration of response, overall survival, and pharmacokinetics of each treatment module, evaluated independently. Exploratory outcomes include tumour and plasma biomarker and resistance analyses, and correlation between biomarker profiles and treatment effect. Safety data will also be reported.

      orchard tip_study design figure.jpg

      Result

      Section not applicable

      Conclusion

      Section not applicable

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