Diadem to Investigate the Activity and Safety of Durvalumab (Diadem)

This is an interventional treatment trial for Pleura Mesothelioma focused on measuring malignant pleural mesothelioma Read More

Inclusion Criteria:

1. Histological diagnosis of advanced unresectable MPM;
2. Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (preferred) or at least 5 unstained slides for central determination of PD-L1 expression;
3. Aged ≥ 18 years;
4. Performance status 0-1 (ECOG);
5. Measurable disease as defined by Modified RECIST v1.1 for MPM;
6. One previous chemotherapy line for MPM, based on pemetrexed plus platinum derivative combination;
7. Previous chemotherapy course concluded at least 4 weeks prior to recruitment;
8. Signed informed consent;
9. Negative pregnancy test. All patients in reproductive age or potential must agree to use effective contraception, as defined by the study protocol for the entire duration of treatment with study drug and for 3 months following its interruption;
10. Patients who have received palliative radiation are eligible if <30% of bone marrow was irradiated and normal hematological function was completely regained;
11. Adequate organ and marrow function as defined below: Haemoglobin ≥ 9.0 g/dL, Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (> 1500 per mm3), Platelet count ≥ 100 x 109/L (>100,000 per mm3);
12. Adequate liver function: Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (except for patients confirmed Gilbert's syndrome, who will be allowed only in consultation with their physician); AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN;
13. Adequate renal function: Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance.

Exclusion Criteria:

1. Radiotherapy with curative intent to thoracic wall (concomitant with or prior to chemotherapy);
2. Severe concomitant illness;
3. History of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, type I diabetes mellitus, vasculitis, or glomerulonephritis;
4. Any other anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent);
5. History of primary immunodeficiency;
6. HIV( Ab anti HIV+), active TB infection , HBV or HCV infection;
7. History of allogeneic organ transplant;
8. History of hypersensitivity to durvalumab or any excipient;
9. Any condition that, in the opinion of the investigator, would interfere with study treatment or patient safety;
10. History of other malignancies (except basal cell carcinoma or cervical carcinoma in situ, adequately treated, melanoma stage one, prostate adenocarcinoma, bladder cancer), unless in remission for 3 years or more and judged of negligible potential of relapse;
11. Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within one year before enrolment, uncontrolled arterial hypertension or arrhythmias;
12. Brain / leptomeningeal involvement;
13. Any previous treatment with a PD-1 or PD-L1 inhibitor, including Durvalumab;
14. AEs from prior anticancer therapy that have not resolved to grade ≤ 1 except for alopecia