Author of

• 30446

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  P1.01 - Advanced NSCLC (ID 158)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall

  • 30548

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    P1.01-89 - A Multicenter Phase 1/2a Trial of CLN-081 in NSCLC with EGFR Exon 20 Insertion Mutations (ID 488)

    09:45 - 18:00  |  Author(s): Leigh Zawel
    • Abstract

    Background
    

    First and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are largely ineffective against EGFR exon 20 insertion mutations (ins20) and, while several novel agents targeting EGFR ins20 are in development (poziotinib, TAK-788), preliminary reports suggest that EGFR-related adverse events are common and may limit long-term efficacy (Heymach, WCLC 2018, Neal WCLC 2018). Targeted therapies which are safe and effective in patients with EGFR ins20 are needed. CLN-081 (also known as TAS-6417) is a novel, orally available EGFR TKI that selectively inhibits ins20 mutant EGFRs (Mol Cancer Ther 2018; 17:1648). In a cell-based assay using genetically engineered cell lines, CLN-081 potently inhibited intracellular phosphorylation of a wide spectrum of ins20 mutant EGFRs. The selectivity for mutant over wild type EGFR (WT/mut ratio) ranged from 4 to 134-fold depending on the specific mutation, representing an unprecedented level of mutant specificity.

    Method
    

    This is an adaptive phase 1/2a trial evaluating CLN-081 as monotherapy in advanced non-small cell lung cancer (NSCLC) harboring EGFR ins20. Dose escalation will proceed initially according to an accelerated titration (AT) design, converting to a rolling six (R6) design based upon pre-specified safety criteria. Cohort expansion in Phase 1 can occur at one or more doses where responses are observed in R6 cohorts. Transition from Phase 1 into Phase 2a is based upon a Simon-Two Stage design. The starting dose will be 60mg. Once daily and twice daily dosing will be explored. Approximately 90 patients will be enrolled. Eligible patients will have advanced, exon 20 insertion mutation positive NSCLC, and at least one prior platinum containing treatment regimen. EGFR ins20 will be identified based on local testing (tissue or plasma). Patients who have discontinued a previous EGFR TKI due to progressive disease will be allowed in AT dose escalation cohorts but will be excluded from R6, and the Phase 1 and 2a expansion cohorts. The primary objectives in Phase 1 are to demonstrate safety and determine the maximum tolerated dose. Secondary Phase 1 objectives include evaluation of PK and preliminary efficacy. The primary objectives in Phase 2a are to define the recommended phase 2 dose and evaluate the overall response rate. The secondary Phase 2a objectives include additional measures of response and confirmation of CLN-081’s safety profile.

    Result
    

    Section not applicable

    Conclusion
    

    Section not applicable