In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e13108-e13108
Abstract:
e13108^ Background: Catumaxomab (anti-EpCAM x anti-CD3) is approved in the EU for the i.p. locoregional treatment of malignant ascites (MA). The peritoneal cavity invaded by epithelial tumor cells provides an environment for tumor-specific, EpCAM-targeted catumaxomab immunotherapy. In order to monitor the local and systemic pharmacodynamic/ pharmacokinetic (PD/PK) profile of catumaxomab, plasma and ascites samples from patients in the CASIMAS study were investigated. Methods: Plasma and ascites samples were collected in patients prior, during and after catumaxomab i.p. infusions. Samples were analysed for a) Selected cytokines (IL-2, -4, -6, -8, -10, and -12, IFN-gamma, TNF-alpha, and GM-CSF) in 20 patients, b) catumaxomab drug levels in 31 patients (14 patients with MA who received all 4 infusions of 10, 20, 50, and 150 µg were evaluable for systemic PK analysis), c) number of EpCAM+ tumor cells in ascites in 11 patients. Results: Drug levels were highest in ascites fluid ranging from 0 to 219.4 ng/mL at day 10 (n=31/31 patients). Low systemic plasma levels were detected in 7/14 patients (median cmax: 623 pg/mL). In 7/14 subjects no catumaxomab was detected systemically. Furthermore, cytokine concentrations in ascites were higher compared to plasma. Mainly IL-6, -8 & -10 and IFN-gamma were detected; in few cases TNF-alpha and IL-2. Whereas IL-4, -12, and GM-CSF were not detected at all. Anti-tumor activity was proven by i.p. tumor cell elimination. Tumor cell count in ascites dropped markedly below baseline. In the majority (7/11) of patients no EpCAM+ tumor cells were detectable after therapy. Before therapy, in 165/166 evaluable patient samples EpCAM+ tumor cells were detected in the ascites fluid. Conclusions: Catumaxomab represents a locoregional immunological i.p. treatment eliminating tumor cells in the peritoneal cavity and thereby effectively controlling MA. Catumaxomab primarily remains in the peritoneal cavity with low systemic exposure. In line with this, cytokines are mainly released locally, at the site of action. These PD/PK results confirm the results obtained in the pivotal phase II/III study.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.e13108
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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