(UroToday.com) The 2026 GU ASCO annual meeting featured a urothelial carcinoma trials in progress session and a presentation by Dr. Zongren Wang discussing EMPOWER01, a phase II study of zanidatamab combined with BCG in HER2-positive high-risk non-muscle invasive bladder cancer. Zanidatamab is a humanized bispecific monoclonal antibody directed against two non-overlapping domains of HER2. Zanidatamab binds adjacent HER2 molecules in trans and initiates distinct HER2 reorganization, induced HER2 capping, and the formation of large HER2 clusters on the cell surface.
Thus, zanidatamab promotes potent CDC and also mediates HER2 internalization and downregulation, inhibition of cell signaling and tumor growth, as well as ADCC and ADCP. As such, HER2-targeted therapies may improve outcomes for patients with HER2-positive cancers. EMPOWER01 was established to evaluate the efficacy and safety of zanidatamab combined with BCG as a novel bladder-preserving treatment for HER2-positive high-risk non-muscle invasive bladder cancer patients.
This open-label phase II study is enrolling BCG-naïve high-risk non-muscle invasive bladder cancer patients with multiple papillary tumors (high-grade Ta or T1 tumors), and all patients are HER2-positive (IHC 3+ or 2+ with FISH+). First, all visible papillary tumors are removed by TURBT, followed by patients receiving zanidatamab (30 mg/kg, ivgtt), every 3 weeks for 1 cycle. Subsequently, patients receive a second TURBT and are administered 4 cycles of zanidatamab (30 mg/kg, Q3W, ivgtt) + 18 instillations of BCG. Specifically, patients are started on an induction course of BCG with 6 instillations every week, followed by maintenance with 3 instillations every 2 weeks and 9 instillations every 4 weeks:
The primary endpoint is recurrence-free survival rate at 12 months, and secondary endpoints are bladder-preservation rate, overall survival, and safety. EMPOWER01 estimated a recurrence-free survival rate at 12 months of no less than 75.5%, and the study will enroll 20 patients.
Presented by: Zongren Wang, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 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 2026 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 26 – Sat, Feb 28, 2026.