(UroToday.com) The 2025 ASCO annual meeting featured a urothelial carcinoma rapid oral abstract session and a presentation by Dr. Xinan Sheng discussing results from a phase 1b/2 study assessing 9MW2821, a novel nectin-4 antibody drug conjugate, combined with toripalimab in treatment-naïve patients with locally advanced or metastatic urothelial carcinoma.
Urothelial carcinoma is a common cancer, with 614,000 new cases and 220,000 deaths of bladder cancer annually worldwide. Nectin-4 is an adhesion molecule that is highly expressed in variety of solid tumors. Previous studies of 9MW2821 have shown promising efficacy and tolerable toxicity in different advanced cancers, especially in urothelial cancer, cervical cancer, esophageal cancer and breast cancer. At the 2025 ASCO annual meeting, Dr. Sheng and colleagues reported preliminary results of 9MW2821 combined with toripalimab in treatment-naïve patients with locally advanced or metastatic urothelial carcinoma.
This is an open-label, multicenter, phase 1b/2 study to evaluate the safety and efficacy of 9MW2821 combined with toripalimab in locally advanced or metastatic urothelial carcinoma. Patients received 9MW2821 on day 1 and day 8 and toripalimab on day 1, 21 days per cycle. The primary objective was safety, and secondary objectives were efficacy, pharmacokinetics and immunogenicity. The trial design is as follows:
As of April 30, 2025, there were 52 patients with locally advanced or metastatic urothelial carcinoma enrolled and had received the combination therapy of 9MW2821 and toripalimab. Of these 52 patients, there were 47 efficacy evaluable patients included in the efficacy analysis set, of which 40 had treatment-naïve locally advanced or metastatic urothelial carcinoma enrolled and received the combination therapy of 9MW2821 (1.25 mg/kg) and toripalimab (240 mg). The median age was 67 years [range: 36-78], 73% patients were ECOG 1, and 55% of primary tumor sites were upper tract urothelial carcinoma:
![The median age was 67 years [range: 36-78], 73% patients were ECOG 1, and 55% of primary tumor sites were upper tract urothelial carcinoma:](/images/com-doc-importer/216-asco-2025/asco-2025-9mw2821-a-novel-nectin-4-antibody-drug-conjugate-combined-with-toripalimab-in-treatment-naive-patients-with-locally-advanced-or-metastatic-urothelial-carcinoma-results-from-a-phase-1b-2-study/image-1.jpg)
To date, the objective response rate was 87.5% (95% CI 73.2-95.8), including a 12.5% complete response rate (confirmed objective response rate was 80%). The disease control rate was 92.5% (95%CI 79.6-98.4):
The objective response rate in selected subgroups was consistent with results in the overall population. Furthermore, objective response rate of subgroups in liver metastasis, bladder cancer and tumor with negative expression of Nectin-4 were 88.2%, 94.4%, 100%, respectively. This demonstrates that different subgroups of treatment-naïve patients could benefit from the combination therapy of 9MW2821 and toripalimab:
The median progression free survival was 12.5 months (95% CI 6.47 – not reached):
The most common treatment-related adverse events were grade 1 or 2, with 42.3% patients experienced treatment-related adverse events of grade 3 or above, including neutrophil count decreased (11.5%). No treatment-related adverse events leading to death occurred, and there were no new safety signals of 9MW2821 or toripalimab observed in this study:
Dr. Sheng concluded this presentation discussing results from a phase 1b/2 study assessing 9MW2821, a novel nectin-4 antibody drug conjugate, combined with toripalimab in treatment-naïve patients with locally advanced or metastatic urothelial carcinoma with the following take home points:
- 9MW2821 combined with toripalimab has demonstrated encouraging efficacy and a manageable safety profile in locally advanced or metastatic urothelial carcinoma
- 9MW2821 + toripalimab may offer a new choice for urothelial cancer patients
- A pivotal phase 3 study of 9MW2821 + toripalimab versus platinum based chemotherapy is ongoing in China (NCT06592326), and the primary endpoints are progression free survival and overall survival
Presented by: Xinan Sheng, MD, Peking University Cancer Hospital & Institute, Beijing, China
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, Chicago, IL, Fri, May 30 – Tues, Jun 3, 2025.