A kidney-sparing approach using disitamab vedotin plus toripalimab for high-risk upper urinary tract urothelial carcinoma in patients with impaired renal function: Preliminary results from a phase II trial.

e16607 Background: Radical nephroureterectomy (RNU) is the gold standard for high-risk upper urinary tract urothelial carcinoma (UTUC). However, for patients with a solitary kidney, renal insufficiency, or bilateral disease, RNU necessitates permanent renal replacement therapy. This phase II trial (NCT06354231) evaluates the clinical activity and safety of Disitamab Vedotin (DV), a HER2-targeted ADC, combined with Toripalimab as a kidney-sparing strategy for this vulnerable population. Methods: This ongoing study enrolls high-risk UTUC patients for whom RNU is clinically unsuitable. The regimen comprises 6 induction cycles of DV (2.0 mg/kg) plus Toripalimab (3.0 mg/kg) Q2W. Patients achieving a response (CR, PR, or SD) proceed to kidney-sparing surgery (endoscopic ablation), followed by consolidation with 12 cycles of DV and 1-year Toripalimab maintenance. The primary endpoint is 1-year kidney-intact disease-free survival (KIDFS). Results: As of the data cutoff, 9 patients were enrolled with a median follow-up of 12.4 months. Baseline HER2 status (IHC) was 2+ (n = 4), 1+ (n = 4), and 0 (n = 1), Among the 9 patients, 7 were evaluable for response. Of the 2 non-evaluable (NE) patients, one withdrew consent for personal reasons after 2 cycles, and one remains awaiting the first assessment. In the evaluable cohort (n = 7), tumor responses during induction included 4 partial responses (PR) and 3 stable diseases (SD). Following endoscopic ablation, the 6-month clinical complete response (cCR) rate was 100% (7/7). The 1-year KIDFS rate reached 100% (4/4) in patients with at least 12 months of follow-up. The safety profile was manageable, with no grade ≥3 treatment‐related adverse event (TRAE) observed to date. The most frequent TRAEs included grade 1 hand-foot syndrome (4/7) and grade 2 hepatic dysfunction (2/7). Conclusions: The combination of DV and Toripalimab demonstrates encouraging preliminary activity and a favorable safety profile in high-risk UTUC. Achieving 100% kidney retention in evaluable cases suggests this paradigm could provide a viable nephron-sparing alternative for patients ineligible for RNU. Continued enrollment will further characterize long-term oncologic and functional outcomes. Clinical trial information: NCT06354231 .