Author of

• 20168

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  P2.04 - Clinical Design, Statistics and Clinical Trials (ID 705)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Clinical Design, Statistics and Clinical Trials
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 23337

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    P2.04-008 - ATLANTIS: Phase III Study of PM01183 with Doxorubicin vs. CAV or Topotecan in Small-Cell Lung Cancer After Platinum Therapy (ID 9326)

    09:30 - 16:00  |  Author(s): A. Farago
    • Abstract
    • Slides

    Background:
    Lurbinectedin (PM01183) is a new compound that blocks active transcription, produces DNA breaks and apoptosis, and affects the inflammatory microenvironment. First signs of synergism with doxorubicin (DOX) and responses, especially in relapsed small cell lung cancer (SCLC) (overall response rate [ORR] ~67%, including about 10% of complete responses [CR]), were reported in a phase I expansion cohort in 21 second-line SCLC patients (ASCO 2015, abstract 7509). Main toxicity was hematological. A lower dose was used to improve safety, and activity was confirmed in an expansion cohort of 27 patients with relapsed SCLC (~37%, with 4% of CR)
    
    Method:
    Multinational (20 countries), multicenter (154 sites), open-label, randomized phase III study of PM01183/DOX vs. a control arm with investigator choice of either standard cyclophosphamide, DOX and vincristine (CAV) or topotecan (T). A total of 600 patients will be randomized (1:1) and stratified according to ECOG performance status (PS), central nervous system (CNS) involvement, previous treatment with antiPD1/antiPD-L1, chemotherapy-free interval and investigator´s choice of control arm. Patients with clinical benefit after 10 cycles of the combination could continue with single-agent PM01183 or CAV, until progressive disease or unacceptable toxicity. An interim safety analysis by an independent data monitoring committee (IDMC) is planned when the first 150 patients have been randomized. Most relevant inclusion criteria includes: age ≥18 years and confirmed diagnosis of SCLC (if primary site is unknown, the patient will be eligible if Ki-67 expression >50%), mandatory previous platinum-containing line (additional immunotherapy is allowed), ECOG PS 0-2, and adequate major organ function (including LVEF >50%). Patients are excluded if chemotherapy-free interval is <30 days, pre-treated with PM01183, DOX or T, symptomatic or steroids-requiring CNS involvement, or any medical condition that might preclude safe compliance with study treatment. Primary objective is to determine a difference in progression-free survival (RECIST v.1.1) by independent review committee. Secondary endpoints include overall survival, survival rates at 12/18/24 months, antitumor response (RECIST v.1.1), duration of response, quality of life, safety, subgroup analyses and pharmacokinetics of PM01183/DOX.
    
    Result:
    The first patient was included in August 2016. An interim safety analysis, requested by the IDMC, was conducted on the first 50 patients randomized and treated with 2 cycles, and resulted in a recommendation to continue the trial unmodified.
    
    Conclusion:
    The ATLANTIS randomized phase III study is currently ongoing. Trial recruitment is expected to be completed at Q1 2018.
    
    

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