The 45th International Society of Urology Annual Meeting (SIU2025) was held in Edinburgh, UK, from October 29 to November 1, 2025. The phase I clinical study data of SIM0237, an anti-PD-L1/IL-15 bispecific fusion protein developed by Simcere Zaiming for the treatment of non-muscle-invasive bladder cancer (NMIBC), were released in an oral presentation at the conference. The monotherapy dose-escalation part data demonstrated favorable safety, tolerability, and anti-tumor activity. The promising early results highlight the potential of SIM0237 in addressing the unmet medical needs of patients with NMIBC.
Bladder cancer is one of the most common malignant tumors, with NMIBC accounting for approximately 75% of newly diagnosed cases. The standard treatments for NMIBC include surgical resection of the tumor followed by postoperative intravesical chemotherapy or Bacillus Calmette-Guérin (BCG) therapy, yet the risk of recurrence and progression remains high. For patients with high-risk NMIBC who do not respond to BCG, the current standard treatment remains radical cystectomy, which is accompanied by a high mortality rate within 90 days post-surgery, especially in elderly patients, and significantly impacts patients' quality of life.
SIM0237 is an anti-PD-L1 monoclonal antibody fused with a potency-reduced IL-15/IL-15Rα sushi domain. This molecule exerts a dual-functional anti-tumor effect by binding to PD-L1 to block the PD-1/PD-L1 immunosuppressive pathway, while simultaneously activating the immune system via IL-15. The attenuated IL-15 increases drug tolerability and exposure. Preclinical studies have shown that SIM0237 exhibits significant anti-tumor activity in human bladder cancer xenograft models.
SIM0237-102 is an open-label, multicenter Phase I/II study. A total of seventeen patients with BCG-unresponsive high-risk NMIBC were enrolled in the monotherapy dose-escalation part. All three studied dose levels demonstrated encouraging anti-tumor activity. All three patients with carcinoma in situ (CIS) NMIBC achieved complete remission (CR), with two patients maintaining their CR status for 6 and 12 months, as of the data cutoff date. Among the 14 patients with papillary-only NMIBC, the median disease-free survival (DFS) was immature, with a 12-month DFS rate of 69.2% (95% CI, 37.3%-87.2%).
SIM0237 demonstrated a favorable safety profile at all three dose levels after intravesical instillation without any dose-limiting toxicity, treatment-related SAE or Grade ≥3 treatment-related AE. The 300 mg dose was selected as the recommended dose for SIM0237 monotherapy. The dose expansion part of SIM0237 monotherapy and dose escalation part of SIM0237 in combination with BCG are in progress.
Preliminary results from the monotherapy dose-escalation part suggest that SIM0237 has the potential to become a novel therapy for NMIBC. Relevant data will be further disclosed at international academic conferences next year.