Study of the Trifunctional Antibody Catumaxomab to Treat Recurrent Symptomatic Malignant Ascites

A multi-center, phase II study of catumaxomab in ovarian cancer patients with recurrent
symptomatic malignant ascites requiring therapeutic paracentesis. Each eligible patient will
receive four ascending doses of catumaxomab, administered intraperitoneally via an indwelling
catheter. Catumaxomab will be administered as a 3-hour constant rate infusion with a dosing
interval of 3-4 days. Each patient will participate in this study for up to 7 months
(includes the baseline therapeutic paracentesis and screening period, 11 to 21 days treatment
period, and up to 180 days/6 months follow-up), with monthly post-study follow-up for the
lifetime of the patient.

Catumaxomab is a trifunctional antibody targeting EpCAM on tumor cells and CD3 on T cells.
Trifunctional antibodies represent a new concept for targeted anticancer therapy. This new
antibody class has the capability to redirect T cells and accessory cells (e.g. macrophages,
dendritic cells (DCs) and natural killer (NK) cells) to the tumor site. According to
preclinical data, trifunctional antibodies activate these different immune effector cells,
which can trigger a complex anti-tumor immune response.

Inclusion Criteria:

- Signed and dated informed consent

- Histologically confirmed diagnosis of epithelial ovarian cancer, peritoneal cancer, or
fallopian tube cancer; any stage at diagnosis [International Federation of Gynecology
and Obstetrics (FIGO) Stages I through IV].

- Progression on or ≤ 12 months after primary platinum-based systemic or intraperitoneal
(IP) chemotherapy OR relapse following reinduction ≥ 12 months after primary
chemotherapy.

- Have refused, failed, or have been deemed not suitable candidates for gemcitabine or
liposomal doxorubicin.

- Recurrent symptomatic malignant ascites requiring therapeutic paracentesis

- At least 1 therapeutic paracentesis within 4 weeks prior to baseline paracentesis

- Age ≥ 18 years

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

- Life expectancy ≥ 16 weeks

- Serum creatinine ≤ 1.5 x upper limit of normal (ULN)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN, and
total bilirubin ≤ 1.5 x ULN

- Absolute neutrophil count (ANC) ≥ 1,500/mm3 and platelet count ≥ 75,000/mm3

- Negative serum pregnancy test result at screening in women of childbearing potential
(applies to patients without documented menopause or sterility).

- Willingness of patients of childbearing potential to use an effective contraceptive
method (i.e., oral contraceptive, cervical cap, diaphragm with spermicide, condom with
spermicide, or intrauterine device) during the study and for at least 6 months after
the last infusion.

Exclusion Criteria:

- Acute or chronic systemic infection

- Exposure to investigational drugs, chemotherapy or radiotherapy 21 days prior to the
first dose of catumaxomab

- Major surgery 2 weeks prior to first dose

- Previous treatment with mouse or rat antibodies

- Known or suspected hypersensitivity to catumaxomab or other monoclonal antibodies

- Body mass index (BMI) < 19 (body weight after paracentesis to be used for calculation
of BMI)

- Serum albumin level < 2.0 g/dL

- Reduced nutritional status requiring predominantly parenteral nutrition (> 50% of
energy intake). Permanent naso-gastric (NG) feeding tube.

- Ileus in a location that precludes paracentesis

- Extensive liver metastases (> 70% organ volume comprises malignancy)

- Documented brain metastases

- History of myocardial infarction, congestive heart failure or relevant cardiac
arrhythmia 3 months prior to the first dose of catumaxomab

- Portal vein obstruction or portal vein thrombosis diagnosed by computed tomography
(CT) scan at screening

- Persistent massive pleural effusion or inadequate respiratory function of any other
etiology (except if related to ascites symptoms) in the opinion of the investigator

- Any other condition which, according to the investigator, results in an undue risk to
the patient by participating in the study

- Prior exposure to catumaxomab