Introduction
Despite standard treatment, NMIBC recurrence remains high, necessitating repeated surgeries and adjuvant therapy. Bel-sar, a novel virus-like drug conjugate (VDC), induces tumor necrosis and enhances anti-tumor immune activation. A phase 2 trial in uveal melanoma showed 80% tumor control at 12 months. This Phase 1 study evaluated the safety and early efficacy of single-dose bel-sar administration during cystoscopy in NMIBC.
Materials & Methods
Following Ethics Committee approval, 16 NMIBC patients received bel-sar (100 µg) 7–12 days before TURBT, either alone (n=5) or with near-infrared (690 nm) light activation (n=11) at two dose levels (100 µg / 200 µg). Tumor and immune response were assessed through central histopathologic evaluation.
Results
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Among 16 patients monitored for safety (56-day follow-up), no drug-related grade 2+ adverse events, serious adverse events, or dose-limiting toxicities were reported.
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In the efficacy group (n=8, light-activated cohorts), 5 had low-grade (LG) and 3 had high-grade (HG) disease.
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A clinical complete response (cCR), defined by the absence of tumor cells in histopathology, was observed in 4/5 LG treated tumors, with 3/5 also achieving cCR in untreated lesions.
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Visual tumor shrinkage was noted in 2/3 HG cases, though tumor cells remained histologically. Strong CD4+/CD8+ T-cell infiltration was detected in treated and non-treated tumors, indicating a urothelial field effect.
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Lymphoid follicles, suggesting adaptive immune activation, were present in 5/7 treated tumors.
Conclusion
Single low-dose bel-sar with light activation induced rapid tumor necrosis and a robust immune response, demonstrating potential as an immune-ablative therapy for NMIBC. The observed cCR in both treated and untreated tumors highlights its ability to generate a field effect. Further studies are required to refine dosing strategies and assess long-term outcomes.
European Association of Urology, 21-24 March 2025, Madrid, Spain
