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Bob T. Li



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    Lunch & Poster Display session (ID 58)

    • Event: ELCC 2019
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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      183TiP - A phase II study of [fam-] trastuzumab deruxtecan (DS-8201a) in HER2-overexpressing or -mutated advanced non-small cell lung cancer (ID 475)

      12:30 - 13:00  |  Author(s): Bob T. Li

      • 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. However, no HER2-targeted therapies are approved for the treatment of NSCLC. [Fam-] trastuzumab deruxtecan (DS-8201a) is a novel HER2-targeted antibody-drug conjugate with a humanized HER2 antibody, a topoisomerase I inhibitor payload, cleavable peptide-based linker, and a high drug-to-antibody ratio of 7 to 8. In an ongoing phase 1 trial, [fam-] trastuzumab deruxtecan (6.4 mg/kg) had a confirmed objective response rate (ORR) of 58.8% (10/17) in HER2-expressing or -mutated NSCLC and 72.7% (8/11) in HER2-mutated NSCLC, with a manageable safety profile (Tsurutani et al, WCLC 2018).

      a9ded1e5ce5d75814730bb4caaf49419 Trial design

      This multicenter, open-label, 2-cohort, phase 2 study will assess the efficacy and safety of [fam-] trastuzumab deruxtecan (6.4 mg/kg once every 3 weeks) in 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). Approximately 80 subjects will be enrolled; 40 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 cohort 1, HER2-overexpression must be assessed and confirmed by central testing based on archival samples. To be eligible for cohort 2, any HER2-activating mutation must be documented based on archival tumor samples. Study treatment will be continued until progressive disease or unacceptable toxicity. The primary endpoint is ORR based on RECIST version 1.1 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. The study will enroll subjects in North America, Europe, and Japan. Recruitment began in May, 2018.

      d9b324a48b043b3d87bc9b3fe620f260 Clinical trial identification

      NCT03505710.

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement

      Editorial assistance was provided by Stefan Kolata, PhD, of AlphaBioCom, LLC.

      934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study

      Daiichi Sankyo, Inc.

      213f68309caaa4ccc14d5f99789640ad Funding

      Daiichi Sankyo, Inc.

      682889d0a1d3b50267a69346a750433d Disclosure

      D. Planchard: Member on the speakers program, Advisory board: AstraZeneca, Boehringer Ingelheim, BMS, Merck, Celgene, Novartis, Pfizer, Roche. R. Shiga, C.C. Lee, K. Wang: Full-time employee: Daiichi Sankyo. P.A. Jänne: Consulting fees, research funding: Acea, Astellas, AstraZeneca, Araxes, ARIAD, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Eli Lilly, Ignyta, Loxo, Merrimack, Pfizer, PUMA, Genentech; Stock: Gatekeeper; Royalties: LabCorp. All other authors have declared no conflicts of interest.

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