(UroToday.com) The 2026 American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting held in Chicago, IL, will host the Kidney and Bladder Cancer - Posters Session. Dr. Zongren Wang will present Abstract 4597: PUNCH03: Preliminary results from a phase II study of DV combined with tislelizumab and BCG in HER2-positive high risk NMIBC.
The rationale for combining disitamab vedotin (RC48), tislelizumab, and BCG in patients with HER2-positive high-risk NMIBC, noting that despite the established role of BCG and emerging activity of PD-1 inhibition in this disease space, there remains an unmet need for more effective bladder-preserving strategies in biologically selected patients. They emphasized that RC48, a HER2-directed antibody-drug conjugate, may provide synergistic activity when combined with immunotherapy and intravesical BCG in HER2-positive tumors.
This open-label phase II study enrolled BCG-naïve patients with HER2-positive (IHC 2+ or 3+) high-risk NMIBC characterized by multiple high-grade Ta or T1 papillary tumors. Following maximal TURBT, patients received induction treatment with RC48 (2.0 mg/kg every 2 weeks for 1 cycle) and tislelizumab (200 mg every 3 weeks for 1 cycle), followed by repeat TURBT. Patients subsequently received maintenance tislelizumab for at least 1 year, in combination with 3–5 cycles of RC48 and a full induction and maintenance BCG schedule consisting of 18 total instillations. The primary endpoint was 12-month recurrence-free survival (RFS), with secondary endpoints including bladder-preservation rate, OS, and safety.
By August 2025, 24 eligible patients had been enrolled. Median age was 63 years (range: 38–85), 75.0% had multiple papillary tumors, 50% had tumors ≥3 cm, and all patients had cT1 disease. HER2 IHC 2+ expression was observed in 58.3% of patients, while 41.7% had IHC 3+ tumors. Median follow-up was 6.1 months (range: 3.1–14.2). The median number of tislelizumab cycles administered was 10, while the median number of RC48 cycles was 6.
All patients completed induction treatment with tislelizumab and RC48. During follow-up, only two patients experienced recurrence, and one patient ultimately underwent radical cystectomy. The bladder-preservation rate was 95.8% (95% CI: 90.7%–100%).
Regarding safety, treatment-related adverse events were predominantly low grade. The most common adverse events of any grade included fatigue (54.2%), alopecia (33%), anorexia (33%), and peripheral neuropathy (16.8%). Importantly, no grade 3–5 treatment-related adverse events were observed.
Key messages:
- Disitamab vedotin combined with tislelizumab and BCG demonstrated encouraging preliminary efficacy as a bladder-preserving strategy in HER2-positive high-risk NMIBC
- The regimen achieved a high bladder-preservation rate of 95.8% with limited early recurrences
- Treatment-related toxicities were manageable, with no grade 3–5 adverse events observed
- These early findings support further investigation of HER2-directed bladder-preserving approaches in biologically selected NMIBC populations
Presented by: Zongren Wang, Department of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Written by: Julian Chavarriaga, MD, Clinical Assistant Professor, Urologic Oncologist, Department of Urology at Penn State Health @chavarriagaj on X during the American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting held in Chicago, IL between May 29th and June 1st, 2026