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Protocol Number: 06-C-0196 
-MORAb-009 is a high-affinity chimeric (mouse/human) monoclonal IgG1/k antibody directed against human mesothelin. It has been shown that mesothelin is over-expressed in pancreatic cancers, mesotheliomas, ovarian cancers and non-small cell lung cancers, while showing little expression in normal tissues except mesothelial cells. -MORAb-009 has been shown to elicit ADCC-mediated killing. Preclinical experiments and early non-human primate toxicology studies indicate that MORAb 009 is a potentially useful anti-cancer agent. Objectives: -To determine the safety of multiple intravenous infusions and the Maximum Tolerated Dose (within the administered range) of MORAb-009 in subjects with mesothelin-expressing tumors. -To establish the serum pharmacokinetics of MORAb-009 in subjects with mesothelin-expressing tumors using enzyme-linked immunosorbent assay (ELISA). -To detect any antibody response (human anti-chimeric antibodies [HACA]) to MORAb-009 at fixed doses in subjects with mesothelin-expressing tumors. -CTC Levels and serum mesothelin levels will be measured as exploratory endpoints to assess the possible usefulness of these parameters as a measure of response to MORAb-009. Only descriptive statistics will be used in correlating these with clinical parameters. Eligibility: -Subjects 18 years of age or older with advanced pancreatic adenocarcinoma, mesothelioma, mesothelin-expressing ovarian or non-small cell lung tumor who have failed standard chemotherapy. -Subjects must have disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) or evaluable by clinical signs/symptoms supported by biomarker, radiologic, or pathologic studies conducted within 4 weeks prior to study entry. Design: -This will be a Phase I, multiple dose, open label, dose escalation cohort. MORAb-009 will be administered as an infusion 1time per week times 4 infusions. Between 18 and 42 subjects will be enrolled with an aim of approximately 21 evaluable subjects. -Eligible subjects will be enrolled into one of six cohorts with an assigned weekly dose range from 12.5 mg/m(2)to 400 mg/m(2). Each higher dose of MORAb-009 will be administered only after the safety of the lower dose has been established. The target Maximum Tolerated Dose (MTD) is the highest dose at which no more than 1 of 6 subjects experiences a dose-limiting toxicity. -Disease progression will be tabulated by dose level using RECIST via CT/MRI measurements at the baseline and final visits.
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National Institutes of Health Clinical Center