9MW2821, a novel Nectin-4 antibody-drug conjugate (ADC), combined with toripalimab in treatment-naïve patients with locally advanced or metastatic urothelial carcinoma (la/mUC): Results from a phase 1b/2 study.

4519 Background: Nectin-4 is an adhesion molecule that is highly expressed in variety of solid tumors. Previous study of 9MW2821 has shown promising efficacy and tolerable toxicity in different advanced cancers, especially in urothelial cancer, cervical cancer, esophageal cancer and breast cancer. Here we report preliminary results of 9MW2821 combined with Toripalimab in treatment-naïve patients with la/mUC. Methods: This is an open-label, multicenter, phase 1b/2 study to evaluate the safety and efficacy of 9MW2821 combined with Toripalimab in la/mUC. Patients received 9MW2821 on D1/D8 and Toripalimab on D1, 21 days per cycle. Primary objective was safety, and secondary objectives were efficacy, pharmacokinetics and immunogenicity. Results: 40 treatment-naïve patients with la/mUC were enrolled and received the combination therapy of 9MW2821(1.25mg/kg) and Toripalimab(240mg). Median age was 66.5 years [36-78], and 73% patients were ECOG 1. 55% primary tumor sites were upper tract urothelial carcinoma. As of Dec 19, 2024, ORR was 87.5% [35/40, 95%CI 73.2-95.8], including 7.5% CR rate (comfirmed ORR was 80%). DCR was 92.5% [37/40, 95%CI 79.6-98.4]. Median PFS and DoR were not reached, 6-month PFS rate and 3-month DoR rate were 79.1% and 100%. Furthermore, ORR of subgroups in liver metastasis, bladder cancer and tumor with negative expression of Nectin-4 were 88.2%, 94.4%, 100%, respectively. These showed that different subgroups of treatment-naïve patients could benefit from the combination therapy of 9MW2821 and Toripalimab. The most common treatment-related AEs(TRAEs) were grade 1 or 2, 23.8% patients experienced TRAEs of grade 3 or above, including neutrophil count decreased (7.1%), rash (4.8%), ALT increased (4.8%), etc. No TRAEs led to death occurred. No new safety signals of 9MW2821 or Toripalimab were observed in this study. Conclusions: 9MW2821 combined with Toripalimab in treatment-naïve patients with la/mUC demonstrated remarkable efficacy and well-tolerated safety profile. A pivotal phase 3 study is ongoing currently. Clinical trial information: NCT06079112 .