Author of

• 11826

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  P2.14 - Poster Session 2 - Mesothelioma (ID 196)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Mesothelioma
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11841

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    P2.14-015 - A randomized, double-blind study comparing tremelimumab to placebo in second and third line treatment of subjects with unresectable pleural or peritoneal mesothelioma (ID 3396)

    09:30 - 09:30  |  Author(s): L. Calabro
    • Abstract

    Background
    Malignant mesothelioma (MM) is an uncommon cancer, caused principally by asbestos exposure. There is no approved treatment after first-line platinum-pemetrexed (Vogelzang, 2003), as no agents have shown survival benefit in this setting (Ceresoli, 2010). Novel approaches are clearly needed. Asbestos exposure induces immunosuppression and immune dysfunction in the mesothelium environment, mainly by a hyper-activation of regulatory T lymphocytes (T-reg) and an over-production of cytokines inhibiting cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells (Maeda, 2010; Kumagai-Takei, 2011; Robinson, 2011). This suggests that agents that target the immune microenvironment may be appropriate to evaluate in MM. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4, CD152) is expressed upon T-cell activation, modulating and eventually switching off T-cell activation. Tremelimumab (treme) binds to CTLA-4 antigen, preventing its negative regulatory signal to T cells. Treme has been investigated in more than 1000 patients in various tumor types. An Italian investigator-sponsored Phase 2 study of Treme in 29 MM patients who progressed on platinum-pemetrexed showed encouraging activity, including promising 1- and 2-year survival rates and a safety profile consistent with that observed across the clinical development program for treme (Calabro et al, 2012). Currently this study has been expanded and is exploring an optimized dosing schedule 10mg/kg on Day 1, every 4 weeks for 6 doses in induction phase, then every 12 weeks in maintenance phase until disease progression or severe toxicity.

    Methods
    Study design: This is an international, Phase 2, randomized, double-blind, placebo-controlled study. Subjects with unresectable pleural or peritoneal MM who have progressed following 1 (first line regimen containing platin plus pemetrexed) or 2 prior chemotherapy regimens will be randomized in a 2:1 ratio to receive either treme or placebo. Randomization will be stratified by EORTC status (low-risk vs high-risk), line of therapy (second vs third), and anatomical site (pleural vs peritoneal). A total of 180 subjects will be enrolled at approximately 150 study centers in multiple countries. Endpoints: Primary endpoint: Overall Survival (OS). Secondary endpoints: durable disease-control rate (DCR); progression-free survival (PFS); effect of treme on patient-reported outcomes (PROs) including disease-related symptoms, pain symptoms, and time to deterioration of disease-related symptoms; overall response rate (ORR) and duration of ORR; safety and tolerability of treme, immunogenicity and pharmacokinetics (PK) of treme in treated subjects. Exploratory objectives: DCR, PFS, ORR, and duration of response based on immune‑related response criteria (irRC); health-related QoL, disease-related symptoms, pain, and health status in subjects with durable clinical activity; biomarkers and their association with treme treatment and clinical outcome.

    Results
    not applicable

    Conclusion
    Current status: The study started recruiting in May 2013. More info is available at ClinicalTrials.gov Identifier NCT01843374.