EMPOWER01: A phase II study of zanidatamab combined with bacillus Calmette-Guerin (BCG) in HER2-positive high-risk non-muscle-invasive bladder cancer (HR NMIBC).

Abstract

TPS899 Background: Zanidatamab was a humanised, bispecific monoclonal antibody directed against two non-overlapping domains of HER2. Zanidatamab binded 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 promoted potent CDC and also mediated HER2 internalization and downregulation, inhibition of cell signaling and tumor growth, as well as ADCC, and ADCP. HER2-targeted therapies may improved outcomes for patients (pts) with HER2-positive cancers. BCG induction and maintenance after transurethral resection of bladder tumor (TURBT) was standard of care in HR NMIBC. Our study was established to evaluate the efficacy and safety of zanidatamab combined with BCG as a novel bladder-preserving treatment for HER2-positive HR NMIBC pts. Methods: This open-label phase II study enrolled BCG-naïve HR NMIBC pts with multiple papillary tumors (high-grade Ta or T1 tumors), and all pts were HER2-positive (IHC 3+ or 2+ with FISH+). Firstly, the papillary tumors should be removed all visible lesions by TURBT. Secondly, pts were administered zanidatamab (30 mg/kg, ivgtt), every 3 weeks for 1 cycle. Then, pts received second TURBT, and pts were administered 4 cycles of zanidatamab (30 mg/kg, Q3W, ivgtt) and 18 instillations of BCG. Specifically, pts were 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 end point was recurrence-free survival (RFS) rate at 12 months. Secondary end points were bladder-preservation rate, OS and safety. Our study estimated a RFS rate at 12 months was no less than 75.5% and the study would enroll 20 pts. Clinical trial information: ChiCTR2200067158.