Author of

• 25904

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  MA15 - Colliding Approaches - EGFR and Immunotherapy (ID 916)

  • Event: WCLC 2018
  • Type: Mini Oral Abstract Session
  • Track: Targeted Therapy
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 13:30 - 15:00, Room 107

  • 26040

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    MA15.03 - PD-L1 Expression in Untreated EGFRm Advanced NSCLC and Response to Osimertinib and SoC EGFR-TKIs in the FLAURA Trial (ID 12989)

    13:40 - 13:45  |  Author(s): Juliann Chmielecki
    • Abstract
    • Presentation
    • Slides

    Background
    

    In the Phase III FLAURA trial (NCT02296125), osimertinib significantly improved PFS relative to SoC EGFR-TKIs (gefitinib/erlotinib) in patients with untreated Ex19del/L858R positive (EGFRm) NSCLC. EGFRm NSCLC tumors can exhibit high PD-L1 expression, an important biomarker for immunotherapy treatment decisions. The frequency and clinical relevance of exhibiting both biomarkers prior to treatment are unclear. We report PD-L1 expression in patients with EGFRm advanced NSCLC and association with clinical outcomes following EGFR-TKI treatment.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    Tissue samples from 994 patients with advanced NSCLC were screened for EGFR Ex19del/L858R mutations for enrolment in FLAURA; 556 were randomized to treatment. 197 tissue-blocks from the screened population (including EGFR mutation-positive and -negative samples) were tested for PD-L1 using the SP263 (Ventana) immunohistochemical assay; positive tumour cell (TC) staining PD-L1 TC≥25% and TC≥1% thresholds were applied. PFS was investigator-assessed, per RECIST 1.1, according to PD-L1-expressers (TC≥1%) or -negatives (TC<1%) in randomized patients.

    4c3880bb027f159e801041b1021e88e8 Result
    

    193/197 blocks had sufficient tumor tissue for staining. 65/193 patients were EGFR mutation-negative. 128/193 patients were EGFR mutation-positive: 106/128 were randomized to treatment (osimertinib: 54; SoC: 52). The table presents PD-L1 expression according to EGFR mutation status. For PD-L1-expressers (TC≥1%), median PFS was 18.4 months for osimertinib and 6.9 months for SoC (HR 0.30 [95% CI 0.15, 0.60]). For PD-L1-negative patients (TC<1%), median PFS was 18.9 months for osimertinib and 10.9 months for SoC (HR 0.37 [95% CI 0.17, 0.74]).

    	PD-L1 TC≥1%, n (%)	PD-L1 TC≥25%, n (%)
    EGFR mutation-negative (n=65)
    Screened population (n=65)	44 (68)	23 (35)
    EGFR mutation-positive (n=128)
    Screened population (n=128)	65 (51)	10 (8)
    Randomized to treatment (n=106)	52 (49)	8 (8)
    Randomized to osimertinib (n=54)	28 (52)	3 (6)
    Randomized to SoC EGFR-TKI (n=52)	24 (46)	5 (10)

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    There was PFS benefit with osimertinib versus SoC regardless of whether tumors were PD-L1-expressers (TC≥1%) or -negatives (TC<1%). Using the TC≥25% threshold, PD-L1 prevalence was lower in EGFR mutation-positive than mutation-negative samples; there were insufficient patients with TC≥25% tumors for PFS assessment.

    These results support the efficacy of EGFR-TKIs, including osimertinib, as first-line treatment of EGFRm advanced NSCLC, irrespective of PD-L1 expression.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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• 25921

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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

  • 26312

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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): Juliann Chmielecki
    • Abstract
    • Slides

    Background
    

    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
    

    Section not applicable

    6f8b794f3246b0c1e1780bb4d4d5dc53

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