Author of

• 31401

  +

  P2.12 - Small Cell Lung Cancer/NET (ID 180)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Small Cell Lung Cancer/NET
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall

  • 31405

    +

    P2.12-04 - CLEPSIDRA: A Phase II Trial Combining Iadademstat with Platinum-Etoposide in Platinum-Sensitive Relapsed SCLC Patients (ID 1243)

    10:15 - 18:15  |  Author(s): Tamara Maes
    • Abstract
    • Slides

    Background
    

    Small cell lung cancer (SCLC), an aggressive neuroendocrine malignancy, shows a dismal prognosis with the current pharmacopeia. Notch is a tumor suppressor repressed in SCLC. Iadademstat is the leading selective LSD1 inhibitor and has been shown to re-activate the NOTCH pathway in SCLC, resulting in the repression of ASCL1, a well-known non-druggable SCLC tumor driver, and to produce robust, and in some cases complete and durable, tumor regression in some chemoresistant PDX models. In a previous Phase I study in acute leukemia, iadademstat was safe and well tolerated, supporting it is a meaningful candidate for combination therapy with other agents. This is the first combo trial in SCLC with a LSD1 inhibitor and the current SoC.

    Method
    

    CLEPSIDRA (EudraCT nº 2018-000469-35) is a Phase II study of iadademstat as a second line treatment in combination with platinum plus etoposide re-challenge chemotherapy in patients with relapsed extensive stage SCLC, that includes biopsy biomarkers expression as inclusion criteria to increase likeliness of response to iadademstat treatment. CLEPSIDRA is an open label single-arm multicenter study to assess for the first time the safety, tolerability, dose finding and efficacy of iadademstat in combination with chemotherapy in SCLC patients. It is planned to enroll up to 36 patients. The study is composed of a dose/regime finding part aimed to establish the recommended dose and regime of the combination, and a second part to assess clinical activity by RECIST criteria.

    Result
    

    The design of the trial and the preliminary results in safety, tolerability and clinical activity as per August 2019 cut-off will be presented and discussed. Preliminary results of the first three subjects with RECIST data available as per April showed a 72% RECIST reduction (from 80 at screening to 43 on cycle 2 and 23 after 4 cycles of treatment) in one subject and stable disease at cycle 2 in the other two subjects.

    Conclusion
    

    Combination of multiple oncological drugs requires careful selection of doses and regimes as their toxicity is often accentuated by the addition of a new component. Neutropenia induced by the etoposide-platinum has to be managed when dosing iadademstat. Current data suggest that these toxicities may be managed in an acceptable manner. The initial clinical responses observed also suggest that the combination of iadademstat with SoC may be clinically effective in second line relapsed SCLC patients.

    Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.