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A phase 2 randomized, double-blind, placebo-controlled study of tremelimumab for second and third line treatment in patients with unresectable pleural or peritoneal mesothelioma
© Krug et al; licensee BioMed Central Ltd. 2013
Published: 7 November 2013
Malignant mesothelioma (MM) is an uncommon cancer, caused principally by asbestos exposure. No treatments after first-line platinum-pemetrexed  have shown survival benefit , thus novel approaches are needed. Asbestos exposure induces immunosuppression and immune dysfunction in the mesothelium environment, mainly by hyperactivation of regulatory T lymphocytes and over-production of cytokines that inhibit cytotoxic T lymphocytes and natural killer cells . Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4, CD152) modulates and eventually switches off T cell activation. Tremelimumab (treme) binds to the CTLA-4 antigen, preventing its negative regulatory signal to cytotoxic T cells. Results from a single arm phase 2 study of treme in 29 patients with MM who progressed on a platinum-based regimen showed promising 1- and 2- year survival rates and a safety profile consistent with previous treme studies . This study has been expanded to enroll 29 patients currently treated with an optimized dosing schedule.
This is a phase 2, randomized, double-blind, placebo-controlled study. Patients with unresectable pleural or peritoneal MM who progressed following 1or 2 prior treatments, including a first-line platinum-pemetrexed regimen, will be randomized in a 2:1 ratio to receive either treme or placebo. Randomization will be stratified by EORTC status (low- vs high-risk), line of therapy (second vs third), and anatomical site (pleural vs peritoneal). Enrollment will include 180 subjects at approximately 150 centers in multiple countries. Recruiting began in May 2013.
Primary: overall survival. Secondary: durable disease-control rate (DCR); progression-free survival (PFS); patient-reported outcomes (pain, disease-related symptoms, and time to deterioration of disease-related symptoms); duration of response and overall response rate (ORR); treme safety profile, immunogenicity, and pharmacokinetics. Exploratory: DCR, PFS, duration of response and ORR based on immune related response criteria, health-related quality of life, disease-related symptoms, pain, and health status in patients with durable clinical activity. The association of biomarkers with treme and clinical outcomes will also be explored.
- Vogelzang NJ: J Clin Onc. 2003, 21: 2636-44. 10.1200/JCO.2003.11.136.View ArticleGoogle Scholar
- Ceresoli GL: Cancer Treat Rev. 2010, 36: 24-32. 10.1016/j.ctrv.2009.09.003.View ArticlePubMedGoogle Scholar
- Maeda M: J Immunotoxicol. 2010, 7: 268-78. 10.3109/1547691X.2010.512579.View ArticlePubMedGoogle Scholar
- Calabrò L: Lancet Oncol. 2013, 14: 1104-1111. 10.1016/S1470-2045(13)70381-4.View ArticlePubMedGoogle Scholar
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