Author of

• 10743

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  P1.10 - Poster Session 1 - Chemotherapy (ID 204)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10800

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    P1.10-057 - Addition of Custirsen, a Clusterin (CLU) Inhibitor, to Docetaxel in Stage IV Non-Small Cell Lung Cancer (NSCLC): Design of the ENSPIRIT Phase 3 Study (ID 1975)

    09:30 - 09:30  |  Author(s): O. Barnett-Griness
    • Abstract

    Background
    Background The cytoprotective chaperone clusterin (CLU) is upregulated in NSCLC and other cancers in response to anticancer therapies, such as docetaxel (DOC). Custirsen inhibits CLU expression, enhances chemotherapeutic activity, and has been shown in vivo to reverse DOC resistance. In a non-randomized, phase 1/2 study, patients with stage IIIB/IV NSCLC who received first-line custirsen with gemcitabine/cisplatin had a median overall survival (OS) of 14.1 months. In early phase studies in castration resistant prostate cancer, custirsen plus DOC was well tolerated and showed encouraging efficacy results. DOC is recommended as second-line chemotherapy for advanced NSCLC with a median OS of only 7-8 months. Treatments that improve OS in advanced NSCLC are greatly needed. ENSPIRIT is designed as a Phase 3 study to assess the clinical benefit of adding custirsen to second-line DOC therapy in advanced or metastatic NSCLC.

    Methods
    Methods ENSPIRIT was initiated in September 2012. Eligible patients in this phase 3, multinational, open-label trial (planned enrollment: 1100) have failed 1 prior line of platinum (PT)-based therapy and have a life expectancy >12 wks; ECOG score of 0-1; and adequate bone marrow, renal, and liver function. Patients receive 21-day cycles of DOC (75 mg/m[2] IV day 1) or DOC plus custirsen (640 mg IV/wk, preceded by 3 doses during a 9-day loading period) until progressive disease (PD), unacceptable toxicity, or withdrawal. Randomization is 1:1 and patients are stratified by gender, NSCLC histology (squamous vs non-squamous), best overall response to the first-line PT therapy (stable disease [SD], complete response [CR], partial response [PR], vs PD), and ECOG score. The primary efficacy measure is OS. Secondary efficacy measures are progression-free survival, objective response (OR: CR or PR), disease control (DC: CR, PR, or SD), and duration of OR and DC. All efficacy analyses are intent to treat. Adverse events and laboratory results will be assessed. Two interim analyses are planned for stopping the trial early based on inadequate evidence of clinical benefit or futility.

    Results
    Results Not applicable.

    Conclusion
    Conclusion This Phase 3 study will assess the potential survival benefit of second-line custirsen and DOC therapy in the treatment of advanced or metastatic NSCLC. This study is sponsored by Teva Branded Pharmaceutical Products R&D, Inc., in collaboration with OncoGenex Pharmaceuticals, Inc.