Immunotherapy with the trifunctional antibody removab leads to significant elimination of tumor cells from malignant ascites in ovarian cancer: Results of a phase I/II study

Abstract

2504 Background: Malignant ascites is the abnormal accumulation of fluid within the peritoneal cavity due to the peritoneal spread of the tumor. It is associated with a poor prognosis and low quality of life. Currently available treatment methods are of limited success. In a phase I/II study we investigated a new concept of ascites treatment based on the intraperitoneal application of the trifunctional antibody removab. Via its two binding arms specific for EpCAM and CD3, and its Fc region, removab binds simultaneously to tumor cells, T cells and antigen-presenting cells resulting in a significant tumor cell killing. Methods: For evaluation of treatment success, we developed an immunofluorescence detection method for monitoring effects on tumor cells within the ascites fluid. Cytospins were prepared from fresh ascites samples before, during and after removab treatment. Tumor cell reduction was monitored with a fluorescence double staining (EpCAM; CK8, 18,19). In addition, tumor cell/leukocyte ratio was determined by EpCAM/CD45 double staining. Results: 23 women with ascites in ovarian cancer (stage IIIb, IIIc and IV) were treated with up to 5 intraperitoneal removab infusions within 13 days using increasing dosages of 5–200 μg. During the treatment, a drastic and continuous decrease of tumor cells within the ascites fluid from 540,000 /10e6 total cells to a mean of 35 /10e6 total cells was observed. Remarkably, the tumor cell/leukocyte ratio was completely reversed after the first low-dose (10 μg) removab infusion. After the last removab infusion, all patients had tumor cell counts below 0.1% to 0%. These findings were associated with a strong reduction of ascites flow from a median of 105 ml/h to 23 ml/h. By the end of observation (day 37), 22/23 patients had no need for further paracentesis. Conclusions: The trifunctional antibody removab may provide a promising tumor targeted option for treatment of malignant ascites. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Trion Research GmbH Trion Pharma GmbH