Randomized, Double-blind Study Comparing Tremelimumab to Placebo in Subjects with Unresectable Malignant Mesothelioma

Prior treatment

• Subjects who failed more than 2 prior systemic treatment regimens for advanced malignant mesothelioma
• Currently receiving systemic corticosteroids or other immunosuppressive medications;
• Subjects should not be vaccinated with live attenuated vaccines within one month prior to starting tremelimumab treatment;
• The last dose of prior chemotherapy or radiation therapy (with the exception of palliative radiotherapy) was received less than 2 weeks prior to randomization;
• Any unresolved toxicity from previous anticancer therapy;
• Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results;
• Concurrent enrollment in another clinical study or receipt of an investigational product within the last 4 weeks (participation in the survival follow-up period of a study is not an exclusion criterion);
• Received any prior monoclonal antibody against CTLA-4, programmed cell death 1 (PD1) or programmed cell death 1 ligand 1 (PD-L1);

Other illness

• History of sarcoidosis syndrome;
• History of chronic inflammatory or autoimmune disease;
• History of other malignancy unless the subject has been disease-free for at least 3 years. Non-invasive cancer history (such as carcinoma in situ [CIS] that has been resected) is allowed;
• Any condition that would prohibit the understanding or rendering of information and consent and compliance with the requirements of this protocol;
• Active or history of diverticulitis. Note that diverticulosis is permitted;
• Active or history of inflammatory bowel disease (eg, colitis, Crohn's), irritable bowel disease, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea. Active or history of systemic lupus erythematosis or Wegener's granulomatosis;

Other

• Employees of the study site directly involved with the conduct of the study, or immediate family members of any such individuals.
• Active, untreated central nervous system (CNS) metastasis;
• Pregnant or breast feeding at time of consent;

• Histologically and/or cytologically confirmed pleural or peritoneal malignant mesothelioma. Disease not amenable to curative surgery;
• Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception for 28 days prior to the first dose of investigational product, and must agree to continue using such precautions for 6 months after the final dose of investigational product;
• Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception from Day 1 through 90 post last dose.
• Age 18 and over at the time of consent;
• ECOG Performance status 0-1;
• Progressed after previous receipt of 1-2 prior systemic treatments for advanced disease that included a first-line pemetrexed (or anti-folate)- based regimen in combination with a platinum agent;
• Recovered from all toxicities associated with prior treatment
• Measurable disease
• Adequate bone marrow, hepatic, and renal function
• Negative screening test results for human immunodeficiency virus (HIV), hepatitis A, B and C.
• Written informed consent and any locally required authorization (eg, HIPAA in the USA, EU Data Privacy Directive authorization in the EU) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations;