(UroToday.com) The 2025 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL between May 30th and June 3rd, 2025, was host to a kidney and bladder cancers poster session. Dr. Xu Chen presented the results of a dose-escalation phase I trial evaluating intravesical disitamab vedotin (RC48) for patients with HER-2 expressing high-risk, non-muscle invasive bladder cancer (NMIBC).
HER2 expression has been associated with poor responses to intravesical BCG in patients with high-risk NMIBC, highlighting an unmet need for effective bladder-sparing treatments in this subgroup. Building on preclinical work (Hong X, Adv Sci, 2023) demonstrating the antitumor activity of disitamab vedotin (RC48) in HER2-expressing orthotopic bladder cancer models, Dr. Chen and colleagues initiated a phase 1 dose-escalation trial to evaluate the safety and preliminary efficacy of intravesical disitamab vedotin in HER2-positive high-risk NMIBC patients who were either BCG-naïve or BCG-unresponsive and unsuitable for radical cystectomy.
This open-label, 3+3 dose-escalation study (NCT06378242) enrolled patients aged 18–75 with histologically confirmed high-risk NMIBC (cTa/T1 ± CIS, N0, M0) and HER2 IHC 1+, 2+, or 3+ status. All patients underwent TURBT within 3 weeks of enrollment. Disitamab vedotin was administered intravesically at doses of 60, 120, or 180 mg once weekly for six weeks (induction), followed by optional monthly maintenance for up to nine total instillations. The primary objective was to determine the safety and tolerability; scheduled efficacy assessments included cystoscopy and ultrasound every 3 months.
Between August 15, 2023, and December 1, 2024, 9 patients were treated across all three dose levels. No dose-limiting toxicities (DLTs) or Grade ≥3 treatment-related adverse events (TRAEs) were observed. The most common TRAEs were:
- Urinary tract infection (56%)
- Pollakiuria (11%)
- Hematuria (11.1%).
At a median follow-up of 12 months (IQR: 9.0–12.3), 2 patients experienced recurrence, but no disease progression occurred. At 6 months, 8 patients were efficacy evaluable, and the RFS and PFS were both 100%. At 12 months, among 6 evaluable patients, RFS was 83.3% (95% CI: 27.3–97.5), and PFS remained 100%.
In conclusion, intravesical disitamab vedotin appears to be safe and well-tolerated in HER2-expressing high-risk NMIBC, with promising early signs of efficacy. No maximum tolerated dose was reached, and further dose exploration continues in the ongoing RC48-C029 study (NCT06378242).
These findings support the continued evaluation of intravesical HER2-directed therapy as a novel bladder-sparing strategy in BCG-unresponsive or BCG-naïve high-risk NMIBC patients with HER2 expression, a historically difficult-to-treat subgroup.
Presented by: Xu Chen, Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; Guangdong Provincial Clinical Research Center for Urological Diseases, China.
Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, Chicago, IL, Fri, May 30 – Tues, Jun 3, 2025.