Data from a phase 1 trial (NCT05316155) indicates that TAR-210, an intravesical delivery system for erdafitinib, is showing early clinical promise in patients with FGFR-altered high- and intermediate-risk non-muscle invasive bladder cancer (NMIBC). The study suggests a potential new approach to treating this challenging disease while minimizing systemic toxicity.
Study Design and Patient Population
The phase 1 study enrolled patients with NMIBC harboring FGFR alterations. Cohort 1 included patients with recurrent high-risk disease (high-grade Ta/T1, papillary only, without carcinoma in situ) who had previously received Bacillus Calmette-Guérin (BCG) and underwent transurethral resection of bladder tumor (TURBT). Cohort 3 consisted of patients with recurrent intermediate-risk disease (low-grade Ta/T1) and target lesions before treatment.
Patients in cohorts 1 and 3 received TAR-210 at approximately 2 mg/day or 4 mg/day during the dose-escalation phase, with device placement every 3 months. Both dose levels were expanded in part 2, the dose-expansion phase, and response was evaluated every 3 months. Treatment continued for up to 1 year if patients were recurrence-free in cohort 1 or experienced a complete response (CR) in cohort 3.
The primary endpoint was safety, while secondary endpoints included recurrence-free survival (RFS), duration of CR, and pathological CR rate.
Promising Efficacy Results
The findings showed a 12-month RFS rate of 90% (median follow-up of 8.9 months) among high-risk NMIBC patients with FGFR alterations (cohort 1; n = 21). The median RFS was not estimable. Two patients experienced recurrence, with no RFS difference between TAR-210 dose levels.
In cohort 3, which included 31 response-evaluable patients with intermediate-risk NMIBC and FGFR alterations, the 12-week CR rate was 90%, with all patients achieving a clinical response. The CR rate remained consistent across dose levels, and 86% of CRs were ongoing at data cutoff. Durable response rates were 100% (95% CI, 100%-100%) at 6 months and 89% (95% CI, 43%-98%) at 9 months.
Expert Commentary
According to Antoni Vilaseca Cabo, MD, adjunct physician of the Urology Service at Hospital Clínic de Barcelona in Spain, recurrence rates for NMIBC patients remain high despite available treatments, underscoring the need for more effective therapies. He noted that FGFR alterations are present in approximately 50% to 80% of patients with advanced bladder cancer and are known oncogenic drivers.
Dr. Vilaseca Cabo explained that while erdafitinib has shown good results in metastatic and advanced urothelial carcinoma, systemic adverse effects were a concern for the NMIBC population. The TAR-210 intravesical delivery system was designed to address this by delivering erdafitinib locally, aiming to reduce systemic toxicities while maintaining efficacy. He highlighted the encouraging data, noting the high response rates and the absence of systemic adverse effects in the study.
Ongoing Research
The MoonRISe-1 study (NCT06319820), a phase 3 trial in patients with FGFR alterations and intermediate-risk NMIBC, is currently underway. Patients will be randomized to receive either TAR-210 or standard of care (gemcitabine or mitomycin C).
