Phase I clinical trial of the chimeric anti-mesothelin monoclonal antibody MORAb-009 in patients with mesothelin-expressing cancers.
Publication/Presentation Date
12-15-2010
Abstract
PURPOSE: MORAb-009 is a chimeric monoclonal antibody that targets mesothelin, a tumor differentiation antigen overexpressed in pancreatic cancer, ovarian cancer, mesothelioma, and other malignancies. We conducted a phase I clinical trial of MORAb-009 in patients with advanced mesothelin-expressing cancers to determine its safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD).
METHODS: Cohorts consisting of 3 to 6 subjects each received MORAb-009 intravenously on days 1, 8, 15, and 22 at progressively increasing doses ranging from 12.5 to 400 mg/m(2). Disease evaluation with computed tomography occurred on day 35. Subjects with responding or stable disease could receive additional cycles of MORAb-009.
RESULTS: A total of 24 subjects were treated including 13 mesothelioma, 7 pancreatic cancer, and 4 ovarian cancer patients. The median number of MORAb-009 infusions was 4 (range 1-24 infusions). At the 400 mg/m(2) dose level, 2 subjects experienced DLT (grade 4 transaminitis and a grade 3 serum sickness). Thus, although there were other contributing causes of these adverse events, 200 mg/m(2) was considered the MTD. Other adverse events at least possibly related to MORAb-009 included 7 drug hypersensitivity events (all grade 1 or 2) and a thromboembolic event (grade 4). Eleven subjects had stable disease. There was a dose-dependent increase in serum MORAb-009 concentration.
CONCLUSION: MORAb-009 is well tolerated and the MTD when administered weekly is conservatively set at 200 mg/m(2). In this group of previously treated patients, 11 subjects had stable disease. Phase II studies of MORAb-009 in different mesothelin-expressing cancers are ongoing.
Volume
16
Issue
24
First Page
6132
Last Page
6138
ISSN
1557-3265
Published In/Presented At
Hassan, R., Cohen, S. J., Phillips, M., Pastan, I., Sharon, E., Kelly, R. J., Schweizer, C., Weil, S., & Laheru, D. (2010). Phase I clinical trial of the chimeric anti-mesothelin monoclonal antibody MORAb-009 in patients with mesothelin-expressing cancers. Clinical cancer research : an official journal of the American Association for Cancer Research, 16(24), 6132–6138. https://doi.org/10.1158/1078-0432.CCR-10-2275
Disciplines
Medicine and Health Sciences
PubMedID
21037025
Department(s)
Hematology-Medical Oncology Division
Document Type
Article