Results of a phase II clinical trial to evaluate a re-challenge of intraperitoneal catumaxomab for treatment of malignant ascites (MA) due to epithelial cancer (SECIMAS).

5582 Background: Catumaxomab is approved in Europe for the i.p. treatment of MA. With a growing number of patients (pts) treated, the question arises, if a re-challenge is feasible and effective despite the immunogenicity of this non-humanised antibody. Methods: Pts were eligible if they received 4 i.p. applications of catumaxomab in the CASIMAS study and benefitted with a puncture free interval of > 60 days. Primary endpoint was to determine the proportion of pts who were able to receive at least 3 catumaxomab applications. Secondary endpoints were the development of human anti-drug antibodies (ADA) as well as the safety profile of a second catumaxomab cycle including a composite safety score (CSS) summarizing the worst CTCAE grades for the main adverse reactions (pyrexia, nausea, vomiting, abdominal pain). Efficacy endpoints were time to puncture (TTPu), overall survival (OS) and puncture-free survival (PuFS). Results: Median age was 59.0 years. 8 out of 9 screened pts were treated with a second cycle of catumaxomab. The primary tumor was ovarian cancer in 5 (62.5%), breast cancer in 2 (25%) and urachal cancer in 1 (12.5%) pts. All 8 (100%) pts received all 4 infusions within 20 days. Median CSS was 3.0 after the second cycle while it was 3.4 after the first cycle in the CASIMAS study for these 8 pts. Only less pts had AEs with CTC >3 (SECIMAS 25%; CASIMAS 70.1%). All 8 (100%) pts were ADA-positive at study entry. ADA levels were consistently higher in the plasma than in the ascites fluid. During treatment, highest ADA values were found on day 10 for ascites and day 11 for plasma up to values of > 1 mg/ml. PuFS was 47.5 days and TTPu 60 days after the second cycle, and 37 days and 102 days, respectively after the first cycle. Median OS was 406.5. Conclusions: This first experience with a re-challenge of catumaxomab in MA, demonstrates a tolerable safety profile without acute allergic reactions, in spite of the high immunogenicity of catumaxomab and the repeated application. Efficacy was not impaired despite ADA response and the advanced disease of the pts. A re-challenge seems feasible for selected pts suffering from recurrent MA after a first cycle of catumaxomab. Clinical trial information: NCT01065246.