Amatuximab for High Mesothelin Cancers

* INCLUSION CRITERIA:
* Female or male subjects, greater than or equal to 18 years of age.
* Histologically-confirmed diagnosis of pancreatic adenocarcinoma, mesothelioma, mesothelin-positive ovarian cancer, or NSCLC. A new biopsy is not required; the diagnostic biopsy sample will be sufficient. IHC confirmation of mesothelin-positivity is not necessary for pancreatic adenocarcinoma and mesothelioma as nearly 100% of pancreatic adenocarcinomas and mesotheliomas express mesothelin. Mesothelin expression in ovarian cancer and NSCLC will be tested by IHC and any degree of positivity (1+, 2+, or 3+) will be accepted.
* Subjects are required to have measurable disease that has progressed through prior therapy and that includes a non-hepatic lesion for imaging that is greater than or equal to 1.5 cm, as defined by Modified Response Evaluation Criteria in Solid Tumors (RECIST).
* Eastern Cooperative Oncology Group (ECOG) performance status or 0, 1, or 2.
* Female subjects of childbearing potential and all male subjects are required to consent to use a medically acceptable method of contraception throughout the study period and for 30 days after amatuximab administration. A barrier method of contraception is required.
* Laboratory and clinical results within the 2 weeks prior to Day of Infusion as follows:

  * Absolute neutrophil count (ANC): greater than or equal to 1.5 times 10(9)/L
  * Platelet count: greater than or equal to 75 times 10(9)/L
  * Hemoglobin: greater than or equal to 9 g/dL
  * Serum bilirubin: less than or equal to 1.5 mg/dL
  * Aspartate transaminase (AST): less than or equal to 3 x upper limit of normal (ULN) (less than or equal to 5 ULN acceptable for pancreatic patients with known liver metastasis only)
  * Alanine transaminase (ALT) less than or equal to 3 times upper limit of normal (ULN) (less than or equal to 5 ULN acceptable for pancreatic patients with known liver metastasis only)
  * Alkaline Phosphatase less than or equal to 5 times ULN
  * Serum creatinine less than or equal to 1.5 mg/dL
* Subjects are required to be willing and able to provide written informed consent.

EXCLUSION CRITERIA:

* Subjects are ineligible to participate in this study if any of the following criteria are met:

  * Known allergy or hypersensitivity to monoclonal antibodies;
  * Prior treatment with amatuximab;
  * Prior treatment with SS1(dsFv)PE38 (SS1P);
  * Known brain metastases;
  * Known prosthetic devices that would prohibit imaging of lesion of interest due to radiographic artifact;
  * Evidence of other active malignancy requiring treatment;
  * Clinically significant heart disease (e.g., congestive heart failure of New York Heart Association Class III or IV, angina not well controlled by medication, or myocardial infarction within 6 months);
  * ECG demonstrating clinically significant arrhythmias. Subjects with chronic atrial arrhythmia, (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia), are eligible;
  * Active serious systemic disease, including active bacterial or fungal infection within 2 weeks before study entry;
  * Active viral hepatitis or symptomatic human immunodeficiency virus (HIV) infection;
  * Treatment within 3 months with immunomodulatory therapy (e.g., interferons, immunoglobulin therapy, Interleukin 1 receptor antagonist (IL-1RA) or systemic corticosteroids). Short-term systemic corticosteroids or topical or intra-articular steroids are acceptable, at the discretion of the Investigator;
  * Chemotherapy, biologic therapy, radiation therapy or immunotherapy within 3 weeks prior to dosing with amatuximab;
  * Breast-feeding, pregnant, or likely to become pregnant during the study.