Trifunctional anti-EpCAM/CD3 bsAb catumaxomab intravesically for high and intermediate risk non muscle invasive bladder cancer (HMR-NMIBC): Interim analysis of a phase I study

BackgroundTrifunctional bsAb Catumaxomab (CAT, anti-EpCAM/CD3) represents a promising drug that effectively eliminates bladder cancer (BC) cell lines in urine. After completion of all 6 CAT instillations and a minimum follow up of 5 months, an interim analysis of the CATUNIBLA Phase I trial (NCT04819399) was performed. Safety, PK/PD and efficacy were analysed.MethodsPts with diagnosed HMR-NMIBC after 1st TUR-B received 6 weekly intravesical CAT instillations at a dose of 50, 70 or 100 μg followed by 2nd TUR-B and standard of care (SoC) including adjuvant instillation. After completion of the dose escalation part I further 17 pts were treated with recommended dose of 70 μg (part II).ResultsNo dose limiting toxicity (DLT) occurred during part I including 10 pts. Recommended dose for part II was 70 μg and further 17 pts were treated excluding 2 drop outs. In total 25/27 (93%) pts received the full CAT dosage. Pts did not experience any drug-related SAE, but procedure-related urinary tract infection was common. All CAT induced AE were mild or moderate (gr 1-2). Serum cytokines were typically not detectable. 41% of pts developed HAMA which was generally low (≤ 1000 ng/ml) and transient peaking around day 42. Systemic CAT was not detected in any pt. CAT instillations led to transient increases of urinary leukocytes and a strong reduction of EpCAM+ tumour cells in urine. Overall tumor-free rate at 2nd TUR-B was 74% with 69% (9/13) of Tis pts showing CR. Assessing the combination of surgery/CAT and BCG/SoC the overall response rate for all pts was 96% (26/27). During a mean follow-up of 13.5 months 4/26 (15%) pts had tumour recurrences. There was one treatment failure (cystectomy) but no tumour progression.ConclusionsIntravesical administration of the trifunctional, anti-EpCAM/anti-CD3 bsAb Catumaxomab is well tolerated in pts with HMR-NMIBC. CAT does not enter the systemic circulation and elicits only low and transient immunogenicity. MTD was not reached and the recommended Ph2 dose was determined at 70 μg. CAT instillation induce a transient increase of local leucocytes and a reduction of EpCAM+ tumor cells in urine. The high CR rate (69%) of Tis pts before BCG treatment is promising.Clinical trial identificationNCT04819399.Legal entity responsible for the studyLindis Biotech GmbH.FundingLindis Biotech GmbH.DisclosureP. Ruf: Other, Personal, Full or part-time Employment: Lindis Biotech GmbH. H. Lindhofer: Financial Interests, Personal, Ownership Interest: Lindis Biotech GmbH. R. Oberneder: Financial Interests, Personal, Coordinating PI: Urological Clinic Munich-Planegg. All other authors have declared no conflicts of interest.