765 Background: As a special subtype of upper tract urothelial carcinoma (UTUC), lower segment ureteral carcinoma (LSUC) is common. Its unique location makes it resectable via distal ureterectomy (DU) while preserving the kidney. However, the high recurrence rate of UTUC makes this treatment strategy potentially risky. Nevertheless, programmed death receptor-1 immune checkpoint inhibitors is becoming a potential option for UTUC. Moreover, given frequent HER-2 expression in UTUC, combining anti-HER-2 antibody–drug conjugates (ADC) with PD-1 ICIs may achieve better treatment efficacy and outcomes. Therefore, to explore efficacy and safety of the new kidney-sparing strategy that neoadjuvant tislelizumab, a type of PD-1 ICIs, combined with Disitamab Vedotin (RC48), a kind of anti-HER-2 ADC, followed by DU for pts with LSUC, we evaluated it in the single-arm, phase II, single-center TRUCE-UTUC01 trial. Methods: In this study, pts with HER-2 expressing (IHC 2+/3+ at baseline pathological specimen) cT1-4N0-2M0 LSUC were enrolled and received 2-3 cycles of neoadjuvant RC48 2.0mg/kg and Tislelizumab 200mg intravenously on days 1, Q3W, followed by distal ureterectomy (DU). The primary endpoint is pathological complete response (pCR, defined as no residual lesions found in the pathological specimen from DU). Secondary endpoints include objective response (OR, including CR and PR according to RECIST 1.1), overall survival (OS), relapse-free survival (RFS), and progress-free survival (PFS). Treatment-related adverse events (TRAEs) are evaluated according to CTCAE v5.0. This trial is registered with ClinicalTrials.gov number, NCT05837806, and is ongoing. Results: 10 pts were enrolled, comprising 7(70%) males, with a median age of 71(IQR 65-77) years. Baseline Her-2 expression was 2+ in 7 (70%) pts, and 3+ in 3 (30%) pts. 1 pts withdrew from the study for refusing surgery. All pts have received no less than 2 cycles of treatment, then completed imaging evaluation, while 9 pts completed pathological assessment. 4 of 9 (44%) pts achieved pCR, 4 of 10 pts achieved ICR, and 7 of 10 pts achieved IOR. The median follow-up time was 51.6 weeks as of October 2025, with no deaths reported. Only 1 pts suffered recurrence and progression. The median RFS/PFS has not yet been reached. The TRAEs of any grade with the highest incidence were alopecia (50%), pruritus (40%) and fatigue (30%). Only 1 (10%) pts experienced grade 3 TRAEs, including fatigue and alanine aminotransferase increase. Conclusions: The neoadjuvant tislelizumab + RC48 followed by DU demonstrates favourable efficacy in HER-2 expressing LSUC with acceptable TRAEs. Our approach indicates that this kidney-sparing strategy for LSUC is feasible and holds potential. Clinical trial information: NCT05837806 .
Chen et al. (Sun,) studied this question.