(UroToday.com) The 2026 GU ASCO annual meeting featured a urothelial carcinoma session and a presentation by Dr. Dingwei Ye discussing a phase 1/2 study of an anti-PD-L1/IL-15 variant fusion protein (SIM0237) in BCG-unresponsive high-risk non-muscle invasive bladder cancer. Treatment options for BCG-unresponsive non-muscle invasive bladder cancer are limited. Anti-PD-1 monotherapy and IL-15 agonist in combination with BCG have shown clinical efficacy in BCG-unresponsive CIS non-muscle invasive bladder cancer.
However, it remains unclear whether targeting both PD-(L)1 and IL-15 has a synergistic effect in non-muscle invasive bladder cancer. SIM0237 is an anti-PD-L1/IL-15 variant fusion protein, with the single agent showing a good safety profile and promising efficacy signal in patients with BCG-unresponsive non-muscle invasive bladder cancer in the dose escalation part. At ASCO GU 2026, Dr. Ye and colleagues reported data from the dose escalation and expansion parts of SIM0237 monotherapy from the ongoing Phase 1/2 study (NCT06186414).
Patients with BCG-unresponsive high-risk non-muscle invasive bladder cancer received intravesical SIM0237 following the standard induction/maintenance treatment schedule. A re-induction course was allowed if the patients had persistent CIS or high-grade Ta at month 3. Key study endpoints included dose-limiting toxicity, safety, tolerability, pharmacokinetics, and efficacy, which was defined as: complete response rate and duration of complete response for CIS non-muscle invasive bladder cancer, disease-free survival, and disease-free survival rate at specific time points for papillary-only non-muscle invasive bladder cancer.
From January 10, 2024, to the data cutoff date of August 8, 2025, a total of 43 patients (10 CIS with or without Ta/T1, 33 papillary-only) have received SIM0237 monotherapy, with 3, 10, and 30 patients at the dose levels of 75 mg, 150 mg, and 300 mg, respectively. The median age was 62 years, with 81% male. The median number of prior BCG doses was 13.
Of the 7 CIS patients who had at least 1 post-baseline tumor assessment, 6 achieved a best response of complete response, and 5 maintained the complete response status. In the 33 papillary-only patients, the median follow-up duration was 4.57 months. The median disease-free survival was immature, with a 12-month disease-free survival rate of 75.4% (95% CI, 48.9%-89.4%).
Treatment-emergent adverse events occurred in 38 (88.4%) patients, and 23 (53.5%) patients had treatment-related adverse events. The majority of treatment-related adverse events were grade 1/2 and limited to the urinary system. There were 9 (20.9%) patients who had grade 3 treatment-emergent adverse events, and 1 (2.3%) had a grade 3 treatment-related adverse event. No grade 4 or 5 treatment emergent adverse events were reported. Four (9.3%) patients had symptomatic adverse events, and one had a treatment-related symptomatic adverse event of urinary bladder hemorrhage and prostatic hemorrhage. Ten (23.3%) patients had dose interruptions due to treatment-emergent adverse events, and 4 (9.3%) had dose interruptions due to treatment-related adverse events. There were no dose-limiting toxicities, immune-related adverse events, or adverse events leading to SIM0237 discontinuation. Pharmacokinetic data showed undetectable systemic exposure of SIM0237 in all 29 patients with serum samples analyzed.
Dr. Ye concluded his presentation discussing a phase 1/2 study of SIM0237 in BCG-unresponsive high-risk non-muscle invasive bladder cancer with the following take-home points:
- Intravesical SIM0237 was safe and well-tolerated, with promising clinical efficacy in patients with BCG-unresponsive high-risk non-muscle invasive bladder cancer
- The phase 3 study of SIM0237 monotherapy in this patient population is being planned
Presented by: Dingwei Ye, Shanghai Medical College, Fudan University, Shanghai, 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.