Neoadjuvant Durvalumab and Tremelimumab With and Without Chemotherapy for Mesothelioma

Exclusion Criteria

• •1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) or previous enrollment or randomization in the present study.
• •2. Participation in another clinical study with an investigational product during the last 3 months.
• •3. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
• •4. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, or other investigational agent) \<28 days
• •5. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction.
• •6. Current or prior use of immunosuppressive medication within 28 days before the infusion with durvalumab or durvalumab + tremelimumab with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone or an equivalent corticosteroid.
• •7. Any unresolved toxicity (\>CTCAE grade 2) from previous anti-cancer therapy from diseases other than MPM.
• •8. Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade 1 for disease other than MPM.
• •9. Known auto-immune conditions requiring systemic immune suppression therapy other than prednisone \< 10 mg daily (or equivalent).
• •10. History of interstitial pneumonitis of autoimmune etiology (including immune checkpoint pneumonitis) which has been symptomatic and/or treatment in the past. Any evidence of current ILD or pneumonitis or a prior history of ILD or non-infectious pneumonitis requiring high-dose glucocorticoids.
• •11. History of primary immunodeficiency.
• •12. History of allogeneic organ transplant.
• •13. Intolerance of anti- PD-1/PD-L1 or CTLA-4 axis drug(s), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including prior therapy with anti-tumor vaccines or other immune-stimulatory anti-tumor agents.
• •14. Concurrent severe and/or uncontrolled medical conditions which may compromise participation in the study, including impaired heart function or clinically significant heart disease.
• •15. A concurrent diagnosis of a separate malignancy is allowed if clinically stable and does not require tumor-directed therapy.
• •16. Known history of HIV seropositivity or known acquired immunodeficiency syndrome (AIDS), hepatitis C virus (allowed if received curative therapy), acute or chronic active hepatitis B infection, or other serious chronic infection requiring ongoing treatment.
• •17. Current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment on day 1 of study drug. Patients receiving prophylactic antibiotics (e.g., for prevention of urinary tract infection or chronic obstructive pulmonary disease) are eligible.
• •18. History of leptomeningeal carcinomatosis.
• •19. Receipt of live attenuated vaccination within 30 days prior to receiving durvalumab or + tremelimumab.
• •20. Female subjects who are pregnant, breastfeeding, or male or female subjects of reproductive potential who are not employing an effective method of birth control.
• •21. Any condition that, in the opinion of the investigator, would interfere with the evaluation of the study treatment or interpretation of subject safety or study results.
• •22. Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation, and/or corticosteroids.
• •23. Subjects with uncontrolled seizures.
• •24. No tissue is obtainable at the time of thoracoscopy.