Author of

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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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    P1.01-41 - A Phase 2 Study of DS-8201a in HER2-Overexpressing or -Mutated Advanced Non-Small-Cell Lung Cancer (ID 12939)

    16:45 - 18:00  |  Author(s): Caleb C. Lee
    • Abstract
    • Slides

    Background
    

    Approximately 30% of non-small-cell lung cancers (NSCLC) are human epidermal growth factor receptor 2 (HER2)-overexpressing (immunohistochemistry [IHC] 2+ or 3+) and approximately 2% have HER2-activating mutations. Although HER2 is considered a potential target for NSCLC, no HER2-targeted therapies are approved for the treatment of NSCLC. DS-8201a is a novel HER2-targeted antibody-drug conjugate with a humanized HER2 antibody attached to a topoisomerase I inhibitor payload (DXd) by a cleavable peptide-based linker, and with a high drug-to-antibody ratio of 7 to 8. In preliminary results from the ongoing phase 1, DS8201-A-J101 trial, DS-8201a (5.6 and 6.4 mg/kg) had a confirmed objective response rate (ORR) of 20.0% (1/5) in HER2-expressing NSCLC (Tsurutani et al, ESMO 2017). In addition to NSCLC, DS-8201a also showed substantial antitumor activity with a manageable safety profile in multiple other HER2-expressing tumors such as breast, gastric, and colorectal cancers.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    This multicenter, open-label, 2-cohort, phase 2 study will assess the efficacy and safety of DS-8201a in subjects with HER2-overexpressing or -mutated unresectable and/or metastatic nonsquamous NSCLC that is relapsed/refractory to standard treatment or for which no standard treatment is available (NCT03505710). Overall, approximately 80 subjects will be enrolled; 40 subjects in each of 2 cohorts (cohort 1: HER2-overexpressing [IHC 3+ or IHC 2+]; cohort 2: HER2-mutated including exon 20 insertions and single-nucleotide variants in kinase, transmembrane, and extracellular domains [eg, L755S, V659E, S310F]). To be eligible for inclusion in cohort 1, HER2-overexpression must be assessed and confirmed by central testing based on archival samples. To be eligible for inclusion in cohort 2, any HER2-activating mutation must be documented based on archival tumor samples analyzed by Clinical Laboratory Improvement Amendment-certified laboratory or equivalent. All enrolled subjects will receive a 6.4 mg/kg dose of DS-8201a once every 3 weeks; study treatment will be continued until progressive disease or unacceptable toxicity. The primary endpoint is ORR based on RECIST version 1.1 (percentage of complete and partial response) by an independent radiologic facility. Secondary efficacy endpoints include progression-free survival, duration of response, disease control rate, and overall survival. Safety assessments include serious and treatment-emergent adverse events, physical examinations, vital signs, and clinical laboratory parameters. The study will enroll subjects in North America, Europe, and Japan. Recruitment began in May, 2018.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Section not applicable

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Section not applicable

    6f8b794f3246b0c1e1780bb4d4d5dc53

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