Fresenius has announced encouraging results in the non-ovarian cancer patient stratum of a phase II/III pivotal study on malignant ascites using the trifunctional antibody removab (catumaxomab).

After positive results in the treatment of patients with ascites from ovarian cancer, the antibody again showed a clear advantage over a therapy with puncture alone. The median puncture-free survival period in the patient group treated with removab was significantly longer compared to the control group and clinically relevant.

The median puncture-free survival was 37 days in the removab group versus 14 days in the control group. In the subgroup of patients with ascites from gastric cancer (51 per cent of all nonovarian cancer patients) the difference was even more marked with a median puncture-free survival of 44 days in the removab group versus 15 days in the control group. All other patients (10 per cent breast, 7 per cent pancreatic, 6 per cent colorectal cancer, 26 per cent others) had a median puncture-free survival of 30 days.

On a pooled basis for both strata (ovarian and non-ovarian cancers) the median puncture-free survival was 46 days in the removab group versus 11 days in the control group. Positive results were also achieved in key secondary endpoints. Of special importance was the length of time between treatment and first therapeutic punctures (median time to the first therapeutic puncture).

In contrast to the primary endpoint, patients who died before the next puncture were not included in this metric. As a result, this secondary endpoint is not affected by the prognosis of these patients at the onset of ascites. The median time to the first therapeutic puncture for all non-ovarian cancers was 80 days. Patients with gastric cancer benefited especially from the treatment. Median time to the first therapeutic puncture was 118 days in the removab group versus 15 days in the control group. For all other patients the median time to the first therapeutic puncture in the removab group was 69 versus 15 days in the control group. On a pooled basis for both strata the median time to the first therapeutic puncture was 77 days in the treatment group versus 13 days in the control group. In addition, the EpCAM-positive tumour cell concentration in the ascites fluid decreased in patients treated with removab. At the same time, an increase in CD45-positive leukocytes was seen. Both results indicate a direct anti-tumour effect of the trifunctional antibody.

Removab showed a very good safety profile in this stratum. This is particularly important as malignant ascites occurs at a very late stage in patients with nonovarian cancers. Drug-related adverse events due to cytokine release were mild to moderate and mostly fully reversible, with fever, nausea and vomiting being the most common. Pathologic increases of liver parameters and undesirable changes in white blood cell counts were also mild to moderate, transient and mostly without clinical relevance.

"These results continue to support the potential of removab. They demonstrate the significant benefit for ascites patients due to non-ovarian cancers even though they have a worse prognosis compared to ovarian cancer. This indicates that removab could also play an important role in the treatment of ascites for all underlying non-ovarian cancers," said Dr Thomas Gottwald, President Fresenius Biotech.

The phase II/III pivotal trial with the trifunctional antibody removab included a total of 258 patients divided in two strata: ovarian cancer (129 patients) and non-ovarian cancers (129 patients). Based on a 2:1 randomization ratio, the removab arm in the non-ovarian stratum included 85 patients, of which 62 received all four doses of 10, 20, 50 und 150 µg each. The intraperitoneal infusions were administered over a six-hour period in intervals of three to four days.

Non-ovarian cancer patients account for about 80 per cent of all malignant ascites cases. The encouraging results of this study significantly increase the number of patients that is potentially eligible for the removab treatment.