Intravesical Disitamab Vedotin (RC48) for HER2-Expressing High-Risk Non-Muscle-Invasive Bladder Cancer: A Single-Arm,...

Area of Science:

• Oncology
• Urology
• Clinical Trials

Background:

• HER2 expression in high-risk non-muscle-invasive bladder cancer (HR-NMIBC) is linked to poor response to Bacillus Calmette-Guérin (BCG) therapy.
• There is an urgent need for novel intravesical treatments for HER2-expressing HR-NMIBC.

Purpose of the Study:

• To evaluate the safety and tolerability of intravesical Disitamab vedotin (RC48) in patients with HER2-expressing HR-NMIBC.
• To assess the preliminary oncological outcomes, including recurrence-free survival (RFS) and progression-free survival (PFS).

Main Methods:

• A single-arm, phase I clinical trial (ChiCTR2300073975) involving nine patients with HER2-expressing HR-NMIBC.
• Patients received intravesical RC48 weekly for 6 weeks (60, 120, or 180 mg doses), followed by optional monthly maintenance doses.
• Safety was assessed by monitoring dose-limiting toxicities (DLTs) and drug-related adverse events (AEs).

Main Results:

• All nine patients completed the induction course without DLTs or grade ≥3 drug-related AEs.
• The most common drug-related AEs were urinary tract infection (55.6%), urinary frequency (11.1%), and hematuria (11.1%).
• At 12 months, RFS was 87.5% and PFS was 100%, indicating promising oncological outcomes.

Conclusions:

• Intravesical RC48 is safe and well-tolerated in HER2-expressing HR-NMIBC patients.
• RC48 demonstrates preliminary efficacy in terms of recurrence and progression.
• Further dose exploration is ongoing to determine the maximum tolerated dose and optimize treatment regimens.