TRION Research GmbH

Intraoperative blood salvage can reduce the need for allogeneic blood transfusions, minimizing immunological risks and infection by reusing the patient's own blood. However, in cancer surgery, a key concern limiting its use is the potential reintroduction of viable cancer cells. Additional risks, such as infection and coagulopathy, have also contributed to its limited adoption. Irradiation of salvaged blood remains an option; however, it is time-intensive and may have detrimental effects on blood cells. These challenges highlight the need for improved technologies to enable safe application in oncological procedures. One such promising tool is CATUVAB®, which removes epithelial cell adhesion molecule (EpCAM)-positive tumor cells from salvaged blood.

In this multicenter, clinical validation study, patients undergoing major surgery for bladder cancer, gastric carcinoma, ovarian carcinoma, pancreatic carcinoma, colon/rectal carcinoma, non-small cell lung cancer, or peritoneal carcinomatosis were included. The primary objective of the study was to elucidate the efficacy of CATUVAB® in depleting intraoperatively salvaged blood of EpCAM-positive tumor cells. Secondary objectives included the determination of residual Catumaxomab antibody amount and cytokine levels in the final erythrocyte concentrate (EC).

203 patients were assessed for eligibility, and 80 were included in the safety analysis, of whom 61 had EpCAM-positive tumor cells in intraoperative blood. The primary efficacy analysis demonstrated a 100 % (95 % CI (95.8 %-100 %)) rate of sufficient depletion of EpCAM-positive tumor cells (p < 0.0001). In 117 out of 131 EC samples (89 %) the catumaxomab concentration was below the limit of quantification. Additionally, cytokines IL-6 and IL-8, typically due to surgical trauma, were significantly reduced (30- to 38-fold) in ECs compared to intraoperative blood.

The study demonstrates the efficacy, safety and feasibility of CATUVAB® for the re-infusion of autologous EC processed by a cell salvage device during high-blood-loss cancer surgeries. These promising results have the potential to re-define the intraoperative blood salvage protocols in cancer surgeries.

Intraoperative blood salvage (IBS) is regarded as an alternative to allogeneic blood transfusion excluding the risks associated with allogeneic blood. Currently, IBS is generally avoided in tumor surgeries due to concern for potential metastasis caused by residual tumor cells in the erythrocyte concentrate.

The feasibility, efficacy and safety aspects of the new developedCatuvabprocedure using the bispecific trifunctional antibody Catumaxomab was investigated in an ex-vivo pilot study in order to remove residual EpCAM positive tumor cells from the autologous erythrocyte concentrates (EC) from various cancer patients, generated by a IBS device.

Tumor cells in intraoperative blood were detected in 10 of 16 patient samples in the range of 69–2.6 × 105but no residual malignant cells in the final erythrocyte concentrates afterCatuvabprocedure. IL-6 and IL-8 as pro-inflammatory cytokines released during surgery, were lowered in mean 28-fold and 52-fold during theCatuvabprocedure, respectively, whereas Catumaxomab antibody was detected in 8 of 16 of the final EC products at a considerable decreased and uncritical residual amount (37 ng in mean).

The preliminary study results indicate efficacy and feasibility of the new medical deviceCatuvaballowing potentially the reinfusion of autologous erythrocyte concentrates (EC) produced by IBS device during oncological high blood loss surgery. An open-label, multicenter clinical study on the removal of EpCAM-positive tumor cells from blood collected during tumor surgery using theCatuvabdevice is initiated to validate these encouraging results.

Transurethral resection of the tumor (TUR-B) followed by adjuvant intravesical treatment with cytostatic drugs or Bacillus Calmette–Guérin (BCG) as standard therapy of non-muscle-invasive bladder cancer (NMIBC) is associated with a high recurrence rate of about 60–70%, considerable side effects and requires close monitoring. Alternative treatment options are warranted. Two patients with epithelial cell adhesion molecule (EpCAM)-positive recurrent non-muscle invasive bladder cancer were treated the first time by an intravesical administration of the trifunctional bispecific EpCAM targeting antibody catumaxomab (total dosage of 470 and 1120 µg, respectively). The binding and killing activity of catumaxomab in urine milieu was evaluated in vitro. In contrast to its previous systemic application catumaxomab was well tolerated without any obvious signs of toxicity. Relevant cytokine plasma levels were not detected and no significant systemic drug release was observed. The induction of a human anti-mouse-antibody (HAMA) reaction was either absent or untypically weak contrary to the high immunogenicity of intraperitoneal applied catumaxomab. Tumor cells that were detectable in urine patient samples disappeared after catumaxomab therapy. Endoscopically confirmed recurrence-free intervals were 32 and 25 months. Our data suggest that intravesical administration of catumaxomab in NMIBC is feasible, safe and efficacious, thus arguing for further clinical development of catumaxomab in this indication.