Intravesical therapy with the trifunctional anti-EpCAM/CD3 bsAb Catumaxomab is well tolerated and shows encouraging preliminary efficacy in patients with high-risk NMIBC (CATUNIBLA phase I trial).

Abstract

e16555 Background: Tx of high-risk NMIBC is challenging due to a high risk of recurrence. Novel therapeutic options are highly anticipated to avoid cystectomy and disease progression. Malignant transitional cells express EpCAM. The trifunctional anti-EpCAM/CD3 bsAb Catumaxomab (CAT) mediates cell killing against human BC. This dose escalating Phase I trial (NCT04819399) investigates the safety of intravesical CAT in high-risk NMIBC. Methods: Following first TUR-B, pts with newly diagnosed high-risk NMIBC were enrolled and received 6 x weekly intravesical CAT instillations, each of 2h duration) at a dose of 50 or 70μg. Subsequently, 2nd TUR-B and adjuvant instillation therapy (tx) was performed as SoC. Here, we report the safety and preliminary efficacy of dose cohorts 1 and 2. Results: 7 Pts are included, 5 with pTa, 2 with pT1 disease. There were 5 concomitant pTis. 6/7 pts received the planned 6 x weekly CAT instillations. 1 pt discontinued after 1 instillation due to recurrent UTI. No DLTs occurred. 28 AEs were observed in 6/7 pts, all of gr 1-2 except two unrelated gr 3 AEs . 2/7 pts had an unrelated SAE each (1 hydronephrosis, 1 recurrent fever after BCG). For 6/7 pts cytokines were below LLQ. In one pt of cohort 2 low amounts of IL-6 and IL-8 were detectable. Weak HAMA responses in 5/6 pts transiently occurred at days 29 and 43. CAT instillations led to transient increases of urinary leukocytes. During and after CAT treatment, there was a strong trend towards reduction of EpCAM+ cells in urine. At 2nd TUR-B tumour persistency was observed in two patients only. Remarkably, 3/5 pTis were no longer detected at 2nd TUR-B. So far, 5/7 pts received adjuvant BCG, 2 pts declined. 7/7 pts achieved CR as best response. While 2/3 pts in the 50 μg cohort had a recurrence, no recurrence was observed in the 70 μg cohort. Conclusions: Intravesical instillations with the trifunctional, anti-EpCAM/anti-CD3 bsAb Catumaxomab are well tolerated in pts with high risk NMIBC. CAT does not enter systemic circulation and elicits only low and transient immunogenicity. The MTD is not reached and dose escalation is still ongoing with cohort 3 (100 μg)(updated results will be presented at meeting). The reduction in EpCAM+ urine cells indicates potential activity of this novel immunotherapy and the high CR rate of Tis at the end of CAT therapy is promising. Clinical trial information: NCT04819399. [Table: see text]