Bulumtatug fuvedotin (BFv; 9MW2821) plus toripalimab in patients with locally advanced or metastatic urothelial carcinoma (la/mUC): Follow-up results from a phase 1b/2 study.

4518 Background: Nectin-4 is an adhesion molecule that is highly expressed in variety of solid tumors, especially in urothelial cancer, cervical cancer, esophageal cancer and breast cancer. BFv is a novel site-specific ADC targeting Nectin-4, and Toripalimab is a novel recombinant humanized anti-PD-1 monoclonal antibody. Previous results of BFv and Toripalimab in la/mUC patients have shown promising efficacy and well-tolerable toxicity. Here we report follow-up results of BFv and Toripalimab in la/mUC patients. Methods: This is an open-label, multicenter, phase 1b/2 study to evaluate the safety and efficacy of BFv combined with Toripalimab in la/mUC. Patients received BFv (1.0 or 1.25mg/kg) on D1/D8 and Toripalimab (240mg) on D1, 21 days per cycle. Primary objective was safety, and secondary objectives were efficacy, pharmacokinetics and immunogenicity. Results: As of 1 Dec 2025 (median follow-up time: 16.0 months), 47 assessable patients with la/mUC were enrolled and received the combination therapy of BFv and toripalimab. 7 of them (3 received BFv 1.0mg/kg; 4 received BFv 1.25mg/kg) have been previously treated for la/mUC and other 40 (all received BFv 1.25mg/kg) were treatment-naïve patients. In the overall population, ORR was 83.0% (95%CI 69.2-92.4), CR rate was 12.8%. All CR patients were still on treatment and the longest treatment duration has already exceeded two years. DCR was 89.4% (95%CI 76.9-96.5), median PFS was 12.9 months (95%CI 6.5-NA) and median DOR was not reach. Median OS also was not reach, OS rate at 18 months was 68.1% (95%CI 52.7-79.4). Subgroup analysis showed significant benefits to all patients, which might indicate that compared to traditional chemotherapy, BFv plus toripalimab could bring patients greater benefits and a longer survival time, especially in those elderly and patients with impaired kidney function. Safety profile was consistent with previous results, and there was no other new safety signals of BFv or toripalimab observed in this study. Conclusions: BFv plus toripalimab in patients with la/mUC demonstrated remarkable efficacy and well-tolerated safety profile. A pivotal phase 3 study is ongoing currently. Clinical trial identification: NCT06592326 , NCT06079112 .