This is a Phase 2b, randomized, double-blind, parallel-group study. Subjects with unresectable pleural or peritoneal malignant mesothelioma will be randomized in a 2:1 ratio to receive either tremelimumab or placebo. Approximately 564 subjects will be enrolled at study centers in multiple countries. The study consists of a screening period, a treatment period, a 90-day follow-up period for safety, and a long-term survival follow-up period.
A Phase 2b, Randomized, Double-blind Study Comparing Tremelimumab to Placebo in Second- or Third-line Treatment of Subjects With Unresectable Pleural or Peritoneal Malignant Mesothelioma
This is a Phase 2b, randomized, double-blind, parallel-group study. Subjects with unresectable pleural or peritoneal malignant mesothelioma will be randomized in a 2:1 ratio to receive either tremelimumab 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). This study plans to use the EORTC to stratify subjects into high or low risk groups in order to ensure balanced randomization to the different treatment groups. For subjects in whom pemetrexed was contraindicated or not tolerated or not an approved therapy (eg, peritoneal mesothelioma), prior therapy with a first-line platinum-based regimen is required. Approximately 564 subjects will be enrolled at study centers in multiple countries.
The study consists of a screening period, a treatment period, and a 90-day follow-up period.
Histologically and/or cytologically confirmed pleural or peritoneal malignant mesothelioma;
Disease not amenable to curative surgery;
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 platinum agent.
Recovered from all toxicities associated with prior treatment, to acceptable baseline status, or a NCI CTCAE Grade of 0 or
1, except for toxicities not considered a safety risk, 7. Measurable diseaseby modified RECIST for pleural mesothelioma or RECIST v1.1 for peritoneal mesothelioma; 8. Adequate bone marrow, hepatic, and renal function determined within 14 days prior to randomization defined as: 9. Negative screening test results for human immunodeficiency virus (HIV), hepatitis A, B and C. 10. 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; 11. 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; cessation of contraception after this point should be discussed with a responsible physician. 2. Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception from Days 1 through 90 post last dose. In addition, they must refrain from sperm donation for 90 days after the final dose of investigational product.
You CAN'T join if...
Subjects who failed more than 2 prior systemic treatment regimens for advanced malignant mesothelioma;
Received any prior mAb against CTLA-4, programmed cell death 1 (PD1) or programmed cell death 1 ligand 1 (PD-L1);
History of chronic inflammatory or autoimmune disease with symptomatic disease within the last 3 years prior to randomization.
Active, untreated central nervous system (CNS) metastasis
Any serious uncontrolled medical disorder or active infection that would impair the subject's ability to receive investigational product;
History of other malignancy unless the subject has been disease-free for at least 3 years;
Pregnant or breast feeding at time of consent;
Any condition that would prohibit the understanding or rendering of information and consent and compliance with the requirements of this protocol;