Date: 2012-06-06
Type of information:
phase: 3b
Announcement: results - ASCO 2012 abstract
Company: Fresenius Biotech (Germany)
Product: catumaxomab (Removab®)
Action mechanism: Catumaxomab is the most advanced Triomab® trifunctional antibody (anti-EpCAM x anti-CD3). These antibodies bind to cancer-associated surface antigens and recruit both T cells as well as accessory cells, such as macrophages, dendritic cells and natural killer cells, to the tumor site. As a result, they provide for a new quality of cancer cell killing, activating both arms of the immune system – the adaptive one with cytotoxic T cells as effectors and the innate one including accessory effector cells.
Disease: malignant ascites due to epithelial cancer
Therapeutic area: Cancer - Oncology
Country: France, Germany, Italy, Spain
Trial
details: The phase 3b CASIMAS study was a two-arm, randomized, open-label, study investigating the safety of a 3 Hour i.p. infusion of catumaxomab with and without prednisolone premedication in patients with malignant ascites due to epithelial cancer. The primary objective of this study was to compare catumaxomab with prednisolone (CP) to catumaxomab without prednisolone (C) as 3-hour intraperitoneal (i.p.) infusion by demonstrating superiority for safety and non-inferiority for efficacy of the CP arm.
219 patients were randomized to catumaxomab plus premedication of 25 mg prednisolone (111 pts) or to catumaxomab alone (108 pts). The primary endpoint was the composite safety score (CSS) summarizing the worst CTCAE grades for the main TEAEs (pyrexia, nausea, vomiting, and abdominal pain). A potential impact of prednisolone on efficacy was assessed by the co-primary endpoint puncture-free survival (PuFS). Further parameters included overall survival (OS) and time to next therapeutic puncture (TTPu).
(http://clinicaltrials.gov/ct2/show/NCT00822809)
Latest
news: The superiority of catumaxomab with prednisolone (CP) for safety was not proven as the mean composite safety score (CSS) was comparable in the two groups (CP: 4.1; C: 3.8 for; p= 0.383).
The median PuFS was slightly lower in CP (30 days) compared to C (37 days). However the hazard ratio (HR) for PuFS (HR: 1.130, p=0.402) as well as the 75% quartiles (CP: 155 days, C: 92 days) were in favour of CP compared to C. The median TTPu was similar in both groups (CP: 78 days; C: 102 days, p= 0.599). The majority of patients (123 pts) had no therapeutic paracentesis prior to death (CP: 54.8%; C; 61.7%, p=0.297). Median OS was longer for CP (CP: 124 days; C: 86 days, p= 0.186) without statistical significance. Conclusions: The CASIMAS results are in concordance with the data of the pivotal study and thus confirm the robustness of the treatment effect of catumaxomab in malignant ascites. The administration of 25mg prednisolone as premedication prior to catumaxomab infusion did not change the safety profile and did not negatively impact the efficacy of catumaxomab. The composite safety score after 3-hour infusion time was comparable to that seen in the pivotal study using 6 hours.
