First Time Intravesically Administered Trifunctional Antibody Catumaxomab in Patients with Recurrent Non-Muscle Invasive Bladder Cancer – Beyond the Abstract

Tumors in non muscle invasive bladder cancer (NMIBC) often occur multifocally, tend to be resistant to chemotherapy, and show a high recurrence rate after their transurethral resection. In a proof-of-concept study for the first time, the T-cell engaging trifunctional antibody CATUMXOMAB was intravesically administered to two patients with recurrent NMIBC. CATUMXOMAB targets the epithelial cell adhesion molecule EpCAM which is expressed in bladder cancer. Contrary to its intravenous or intraperitoneal application, the antibody was exceptionally well tolerated. No significant cytokine release or systemic antibody exposure was observed.

To evaluate the efficacy of this new approach, Trion Research developed a method for the detection and quantification of EpCAM-positive tumor cells in urine. Cells in urine fluid from cancer patients are spun down, washed, and stained with EpCAM and cytokeratin-specific markers and evaluated by computerized fluorescence microscopy. After catumaxomab therapy, tumor cells in urine samples disappeared. Therefore, this method can be applied to monitor drug efficacy during and after therapy and may be used as an early indicator of relapse.

The experience gained from these investigations was used for the design of a clinical trial program in this cancer indication with a high unmet medical need. A phase I study has been started in Germany (Catunibla, NCT04819399) and a phase I/II study in China (LPO190512, NCT04799847) was approved by the Chinese authorities recently. The clinical development of CATUMXOMAB aims to reduce the rate of radical cystectomy and the recurrence and progression rate of high-risk NMIBC. Tumor-infiltrating lymphocytes and increased leucocyte numbers in urine fluid after transurethral resection may serve as a source of available immune effector cells for a targeted attack of residual tumor tissue and cells by intravesically applied CATUMAXOMAB. Further immunological investigations are warranted.

Written by: Peter Ruf, Head of Antibody Development, Trion Research GmbH, Am Klopferspitz 19, Martinsried, Germany

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