Author of

• 17842

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  P2.06 - Poster Session with Presenters Present (ID 467)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 17863

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    P2.06-021 - Efficacy and Safety of ASP8273 versus Erlotinib or Gefitinib as First-Line Treatment in Subjects with EGFR<Sup>Mut+</Sup> NSCLC (ID 4148)

    14:30 - 14:30  |  Author(s): A. Keating
    • Abstract

    Background:
    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown antitumor efficacy and prolonged progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC) harboring EGFR activation mutations; however, acquired resistance often develops limiting clinical efficacy. ASP8273 is an irreversible, once-daily (QD), orally available TKI with activity against both activating and resistance EGFR mutations (ex19del, L858R, T790M). Preliminary findings from Phase 1 and Phase 2 trials in the US, Japan, Taiwan, and Korea have demonstrated antitumor activity and overall tolerability of ASP8273 at doses of 100mg–300mg.
    
    Methods:
    This global, multicenter, open-label, randomized, Phase 3 study will enroll ~600 adult subjects with Stage IIIB/IV NSCLC with EGFR-activating mutations (ex19del or L858R, with or without T790M) who have not been treated with an EGFR inhibitor TKI (NCT02588261). Subjects will be randomized 1:1 to treatment with either 300mg oral ASP8273 QD or erlotinib/gefitinib. Each site will select a comparator drug (150mg erlotinib QD or 250mg gefitinib QD) at the beginning of the study. Randomization will be stratified by ECOG status (0, 1, and 2), EGFR mutation (ex19del, L858R), comparator selected (erlotinib vs gefitinib), and race (Asian vs non-Asian). Subjects will not be enrolled if they harbor both ex19del and L858R. All subjects will begin treatment on Day 1 Cycle 1 and will continue on 28-day continuous dosing cycles until the subject discontinues (eg, due to radiologic progression as determined by RECIST or unacceptable toxicity). Dose reductions will be allowed for ASP8273 and erlotinib, but not for gefitinib. The primary study objective is PFS as assessed by independent radiological review (IRR); secondary study objectives are overall survival, best overall response rate, disease control rate and duration of response by IRR, safety/tolerability, and patient quality of life. An independent Data Monitoring Committee will oversee trial safety and the interim futility analysis. Enrollment for the trial began 26 February 2016; 46 subjects have been randomized as of 17 May 2016.
    
    Results:
    Section not applicable
    
    Conclusion:
    Section not applicable
    
    

• 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)

  • 18460

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    P3.02b-086 - ASP8273 Tolerability and Antitumor Activity in TKI-Naïve Japanese Subjects with EGFRmut+ NSCLC: Preliminary Results (ID 4126)

    14:30 - 14:30  |  Author(s): A. Keating
    • Abstract

    Background:
    ASP8273, an orally administered epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that inhibits EGFR-activating mutations, has demonstrated clinical activity in ongoing Phase 1/2 studies in subjects with EGFR mutation-positive non-small cell lung cancer (NSCLC).
    
    Methods:
    EGFR TKI-naïve adult subjects (≥20 years) with EGFR mutation-positive metastatic or advanced unresectable NSCLC were enrolled in this ongoing, open-label, Phase 2 single-arm study conducted in Japan (NCT02500927). Subjects received once-daily ASP8273 300 mg until discontinuation criteria were met. The primary endpoint was tolerability; the secondary endpoint was antitumor activity (defined by RECIST v1.1).
    
    Results:
    As of 23 February 2016, 31 subjects (12M/19F; median age 64 years [range: 31–82]) with EGFR mutation-positive NSCLC have been enrolled; 25 subjects (81%) were still on study. Based on local testing, 27 (87%) of the 31 enrolled subjects had an ex19del (n=13, 42%) or a L858R (n=14, 45%) EGFR activating mutation; 4 subjects (13%) had other EGFR activating mutations, including 2 subjects (6%) with L861Q. Moreover, 3 subjects (10%) were found to have both an activating mutation as well as the T790M resistance mutation. Tolerability of ASP8273 is presented in Table 1; gastrointestinal disorders were the most commonly reported treatment-emergent adverse events (eg, diarrhea [n=24, 77%], nausea [n=12, 39%], and vomiting [n=8, 26%)]). All subjects had at least 1 post-baseline scan; 1 subject (3%) achieved a confirmed complete response, 13 subjects (42%) had a confirmed partial response, and 15 subjects (48%) had confirmed stable disease (disease control rate: 94% [n=29/31]) per investigator assessment. Figure 1
    
    
    
    Conclusion:
    These preliminary data showed that ASP8273 300 mg is generally well tolerated and demonstrates antitumor activity in TKI-naïve Japanese subjects with EGFR mutation-positive NSCLC.