Amatuximab for High Mesothelin Cancers

Background:

- Amatuximab is a high-affinity monoclonal IgG antibody raised against human mesothelin.

- Mesothelin is a glycosyl-phosphatidyl inositol-linked membrane glycoprotein thought to
be involved in tumor metastasis

- Mesothelin is over-expressed in many cancers

Objectives:

-The primary objective is to determine the biodistribution of radiolabeled amatuximab in
tumor and nontumor tissues in subjects with mesothelin over-expressing cancers including
mesothelioma, pancreatic, ovarian, and non small cell lung cancer.

Eligibility:

- Female or male subjects greater than or equal to 18 years of age;

- Histologically confirmed mesothelin-expressing cancer;

- Transaminases less than or equal to 3 times ULN for mesothelioma, non small cell lung
and ovarian cancer;

- Transaminases less than or equal to 5 times ULN for pancreatic cancer with known liver
metastasis.

Design:

- This is a single-center, single-dose, open-label, pilot study of MORAb-009 in
approximately 20 subjects with mesothelin expressing tumors.

- Indium-radiolabeled MORAb-009 (5mCi) will be administered.

- Serial single photon emission-computerized tomography imaging will be performed to
determine binding to tumor and nontumor tissue.

- Subjects will be observed closely for safety and possible development of anti-MORAb-009
antibodies.

- Pharmacokinetics of radiolabeled antibody will be determined with imaging over time.

- 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.