Safety and Therapeutic Efficacy of the Lewis Y Carbohydrate Specific Humanized Antibody MB311 in Patients with Malignant Effusion

Abstract

Purpose: Investigation of safety and tolerability as well as therapeutic efficacy of the LeY specific humanized mAb MB311 in cancer pts with malignant effusions in a Phase II clinical trial. Experimental Design: An openlabel, single treatment arm, uncontrolled study with MB311 (100 mg per dose, intravenous infusion on day 1 and 7) in pts with malignant effusion (ascites or pleural effusion) was conducted with the primary objective to examine safety and tolerability as well as pharmacokinetics. Secondary objectives were assessment of pharmacodynamics, volumetric measurement of the malignant effusion and obtaining data for several immunological parameters. Results: Five pts (2 pts with gastric cancer and malignant ascites, 3 pts with breast cancer and malignant pleural effusion/ascites) have completed the study. MB311 was well tolerated with only two pts showing the easily manageable side effects nausea, vomiting (up to grade 2) and one episode of skin rash (grade 2) after the first application. Data of 4 pts were available for evaluating immunologic results and efficacy. In all pts significant levels of MB311 could be detected in the systemic blood circulation and the effusion leading to increased infiltration of CD45 positive immune cells (4/5 pts) and resulting in a reduction of tumor cell counts as detected by immunocytochemistry of effusion samples in 3/5 pts). Most interestingly, the pt with the highest LeY positive tumor showed a significant reduction of effusion volume after treatment—this decrease was also evident for Her2/neu positive tumor cells which were dramatically reduced after MB311 treatment in this breast cancer pt. Conclusion: MB311 was well tolerated in patients with malignant effusions, permeated into malignant effusion and attracted immune cells leading to decreased tumor cell counts in the effusion. In the case of strong LeY expression of malignant cells in the effusion a pronounced decrease in LeY, EpCAM and Her2/neu positive tumor cells and a significant reduction of the effusion volume could be demonstrated.