NGR015: Randomized Double-blind Phase III Study of NGR-hTNF Plus Best Investigator's Choice (BIC) Versus Placebo Plus BIC in Previously Treated Patients With Advanced Malignant Pleural Mesothelioma (MPM)

Inclusion Criteria:

- Age ≥ 18 years

- Histologically or cytological confirmed malignant pleural mesothelioma of any of the
following subtype: epithelial, sarcomatoid, mixed, or unknown

- Prior treatment with no more than one systemic pemetrexed-based chemotherapy regimen
administered for advanced or metastatic disease. Prior use of a biological agent in
combination with a pemetrexed-based regimen and prior administration of intrapleural
cytotoxic agents are allowed. Patients who have previously received anthracyclines
should not receive doxorubicin

- ECOG Performance Status 0 - 2

- Life expectancy of ≥ 12 weeks

- Adequate baseline bone marrow, hepatic and renal function, defined as follows:

1. Neutrophils ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L; hemoglobin ≥ 9 g/dL

2. Bilirubin ≤ 1.5 x ULN

3. AST and/or ALT ≤ 2.5 x ULN in absence of liver metastasis or ≤ 5 x ULN in
presence of liver metastasis

4. Serum creatinine < 1.5 x ULN

- Measurable or non-measurable disease according to MPM-modified RECIST criteria

- Patients may have had prior therapy providing the following conditions are met:

1. Surgery: wash-out period of 14 days

2. Systemic and radiation anti-tumor therapy: wash-out period of 28 days

- Patients must give written informed consent to participate in the study

Exclusion Criteria:

- Patients must not receive any other investigational agents while on study

- Patients with myocardial infarction within the last six months, unstable angina, New
York Heart Association (NYHA) grade II or greater congestive heart failure, or
serious cardiac arrhythmia requiring medication

- Uncontrolled hypertension

- QTc interval (congenital or acquired) > 450 ms

- History or evidence upon physical examination of CNS disease unless adequately
treated (e.g., primary brain tumor, any brain metastasis, seizure not controlled with
standard medical therapy, or history of stroke)

- Patients with active or uncontrolled systemic disease/infections or with serious
illness or medical conditions, which is incompatible with the protocol

- Known hypersensitivity/allergic reaction to human albumin preparations or to any of
the excipients

- Any psychological, familial, sociological or geographical condition potentially
hampering compliance with the study protocol

- Pregnancy or lactation