Author of

• 15577

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  P3.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 226)

  • Event: WCLC 2015
  • Type: Poster
  • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)

  • 15591

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    P3.08-014 - COMMAND: A Phase 2 Randomized, Double-Blind, Study of Defactinib (VS-6063) as Maintenance Therapy in Malignant Pleural Mesothelioma (ID 2847)

    09:30 - 09:30  |  Author(s): M. Joseney-Antoine
    • Abstract

    Background:
    Malignant pleural mesothelioma (MPM) is an aggressive tumor in the pleural lining of the lung. Median OS with frontline chemotherapy of pemetrexed/cisplatin (pem/cis) is ~12 months. There is no established second line therapy. Pem/cis has been shown to enrich cancer stem cells (CSCs) in tumors. Focal adhesion kinase (FAK) inhibitors have been found to decrease CSCs in mesothelioma models. The use of a FAK inhibitor in a maintenance setting after frontline chemotherapy may therefore extend survival of MPM patients. Furthermore, approximately 40% of MPM tumors exhibit disruption of the NF2 tumor suppressor gene by mutation and/or deletion resulting in lack of expression of functional merlin protein. Mesothelioma cell lines that lack merlin are more sensitive to FAK inhibitors than those with wild type merlin. This Phase 2 study will determine if defactinib (VS-6063), an oral inhibitor of FAK, provides superior clinical benefit compared with placebo as maintenance treatment in patients with MPM following frontline pem/platinum therapy.
    
    Methods:
    COMMAND is a multinational, randomized, double-blind, placebo-controlled trial. Approximately 370 patients with PR or SD following ≥4 cycles of frontline pem/platinum therapy will be enrolled. Patients will receive defactinib 400 mg BID or matched placebo. Randomization will be stratified by merlin status, as determined by immunohistochemistry. Primary endpoints include OS and PFS. An adaptive enrichment design at the interim analysis (projected to occur in Q2 2015) may restrict patients to those with low merlin protein expression if greater benefit is observed among this subpopulation. Secondary endpoints include patient-reported outcomes, objective response and safety and tolerability. The study is currently enrolling across 15 countries. Clinical trial: NCT01870609.
    
    Results:
    Not applicable
    
    Conclusion:
    Not applicable