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
Overview
- Phase
- Phase 2
- Intervention
- Tremelimumab
- Conditions
- Unresectable Pleural or Peritoneal Malignant Mesothelioma
- Sponsor
- MedImmune LLC
- Enrollment
- 571
- Locations
- 104
- Primary Endpoint
- Overall Survival (OS)
- Status
- Active, not recruiting
- Last Updated
- last month
Overview
Brief Summary
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.
Detailed Description
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, a 90-day follow-up period for safety, and a long-term survival follow-up period.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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,
- •Measurable diseaseby modified RECIST for pleural mesothelioma or RECIST v1.1 for peritoneal mesothelioma;
- •Adequate bone marrow, hepatic, and renal function determined within 14 days prior to randomization defined as:
- •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;
Exclusion Criteria
- •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;
- •Active or history of diverticulitis;
- •Active or history of inflammatory bowel disease, irritable bowel disease, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea. Active or history of systemic lupus erythematosus or granulomatosis with polyangiitis;
Arms & Interventions
Tremelimumab
Tremelimumab
Intervention: Tremelimumab
Placebo
Placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: 3 years.
Overall survival (OS) by treatment arm
Secondary Outcomes
- OS Rate at 18 Months by Treatment Arm(18 months)
- Progression-free Survival by Treatment Arm(Time from randomization to disease progression or death, whichever occurs first, assessed up to 3 years.)
- Overall Response Rate by Treatment Arm(Time from randomization to best response to treatment, assessed up to 3 years.)
- Duration of Response by Treatment Arm(Duration of response from the first documentation of objcetive response (confirmed CR or PR) to the first documented disease progression, assessed up to 14 weeks after the initial response.)
- Disease Control Rate by Treatment Arm(Time from randomization to disease progression or death, whichever occurs first, assessed up to 3 years.)
- Durable Disease Control Rate by Treatment Arm(Time from randomization to disease progression or death, whichever occurs first, assessed up to 3 years.)
- Number of Participants Reporting Any Adverse Event(Day 1- 90 days post dose)
- Number of Participants Reporting Any Serious Adverse Events(Day 1 to 90 days post dose)
- Number of Participants With Positive Anti-drug Antibodies(Week 5)