BACKGROUND:Treatment options are limited in non-muscle-invasive bladder cancer (NMIBC) that recurs after intravesical chemotherapy or Bacillus Calmette-Guérin (BCG). TAR-210 is a novel intravesical drug delivery system designed to provide local, continuous release of erdafitinib (selective pan-FGFR tyrosine kinase inhibitor) within the bladder while limiting systemic toxicities. This open-label, multicenter phase 1 study (NCT05316155) evaluated the safety, pharmacokinetics, and efficacy of TAR-210 in patients with NMIBC whose tumors harbor select FGFRalt. METHODS:
FGFRalt were identified in tumor tissue or urine cell-free DNA. Cohort 1 patients had recurrent, BCG-experienced high-risk NMIBC (high-grade Ta/T1; papillary only) and refused or were ineligible for radical cystectomy. Cohort 3 patients had recurrent, intermediate-risk NMIBC (Ta/T1) with history of only low-grade papillary disease. Before treatment, Cohort 1 patients must have all visible disease resected; Cohort 3 requires the presence of visible tumors. TAR-210 systems with two different erdafitinib release rates were evaluated. Response is assessed every 3 months with continued treatment for up to 1 year if recurrence-free (Cohort 1) or in complete response (CR) (Cohort 3).
RESULTS:
As of August 29, 2023, 16 patients in Cohort 1 and 27 patients in Cohort 3 have been treated; 11 and 15 patients, respectively, had ≥1 response assessment. Eighty-two percent in Cohort 1 were recurrence-free; 87% in Cohort 3 achieved CR (Table). Most common treatment-related adverse events (TRAE) were grade 1/2 lower urinary tract TRAEs. There were no dose-limiting toxicities. No deaths were reported. Two patients discontinued due to TRAEs of low-grade urinary symptoms, and one patient had serious TRAEs of pyelonephritis and sepsis. Pharmacokinetics data showed sustained erdafitinib concentrations in urine with very low plasma exposures. Initial results are reported; updated data (≈47 response evaluable patients) will be included in the presentation. CONCLUSIONS:
TAR-210 appears safe and well tolerated with predominantly low-grade urinary system TRAEs and high CR rate and recurrence-free survival in patients with NMIBC with FGFRalt. Results justify further study of targeted treatment of erdafitinib using a novel intravesical delivery system in early-stage bladder cancer.
| Table: Efficacy outcomes and treatment exposure | |
| Cohort 1 (n=11 with response assessment) | |
| RF, n (%) | 9 (81.8) |
| Median RFS (95% CI), mo | NE (2.96-NE) |
| Cohort 3 (n=15 with response assessment) | |
| CR, n (%) | 13 (86.7) |
| Median duration of CR (95% CI), mo* | NE (NE-NE) |
| Both Cohorts (n=43 all-treated) | |
| Median duration of treatment exposure (range), mo | 3.7 (0-12) |
| Total duration of treatment, n (%) | |
| ≥0-<3 mo | 18 (41.9) |
| ≥3-<6 mo | 13 (30.2) |
| ≥6-<9 mo | 6 (14.0) |
| ≥9-<12 mo | 5 (11.6) |
| ≥12 mo | 1 (2.3) |
| CI, confidence interval; CR, complete response; mo, months; NE, non-estimable; RF, recurrence-free; RFS, recurrence-free survival. *All CR in cohort 3 were ongoing as of data cutoff. |
