Early Efficacy and Exploratory Biomarker Data of Bel-sar in Patients with Intermediate-risk and High-risk Non–muscle-invasive Bladder Cancer

Background and objective Despite available therapies, patients with non–muscle-invasive bladder cancer (NMIBC) are impacted by recurrence and progression risk. Bel-sar (belzupacap sarotalocan) is a first-in-class virus-like drug conjugate composed of a tumor-targeting virus-like particle linked to a photoactivatable dye, inducing proimmunogenic tumor cell death and antitumor immune response. We report clinical and exploratory immune biomarker data from a phase 1 study in intermediate-risk and high-risk NMIBC. Methods Seventeen participants received focally injected bel-sar (100–200 µg) without ( n = 5) or with ( n = 12) light activation, followed by transurethral resection of bladder tumor (TURBT; 7–12 d later). Safety, feasibility, tolerability, and preliminary efficacy were assessed. Multiplex immunofluorescence was performed on paired tumor specimens from five responders receiving light-activated bel-sar. Key findings and limitations Bel-sar was well tolerated, with only grade 1 adverse events, and no grade ≥2, serious, or dose-limiting toxicities. Among 10 efficacy-evaluable patients receiving light activation, four of five low-grade tumors achieved complete response. Responses were also observed in high-grade and untreated tumors, suggesting a urothelial field effect. Immune profiling demonstrated conversion of immune-cold or exhausted tumors into immunogenically primed tumors, with tertiary lymphoid structure formation, expansion of cytotoxic and memory CD4+ T cells, and marked natural killer cells and eosinophils recruitment. Limitations include the small sample size and short follow-up. Conclusions and clinical implications Bel-sar demonstrated focal administration feasibility, a favorable safety profile, and encouraging preliminary efficacy in NMIBC, with robust immune activation in treated and untreated tumors. These findings support bel-sar’s continued development as a therapy combining local tumor eradication with durable immune surveillance.