TAR-210 shows strong initial activity in FGFR-altered NMIBC

The erdafitinib (Balversa) intravesical delivery system TAR-210 was safe and showed strong initial efficacy in patients with high- and intermediate non–muscle-invasive bladder cancer (NMIBC) with select FGFR alterations, according to findings from a phase 1 study (NCT05316155) presented during the 2024 American Urological Association Annual Meeting.¹

Response-evaluable patients with intermediate-risk NMIBC and FGFR alterations experienced a 12-week complete response rate of 90%, with 100% of patients experiencing a clinical response.

At a median follow-up of 8.9 months, the estimated 12-month recurrence-free survival (RFS) rate was 90% among patients with high-risk NMIBC and FGFR alterations (cohort 1; n = 21); the median RFS was not estimable (NE). Notably, only 2 patients experienced recurrence and there was no difference in RFS between TAR-210 dose levels.

Additionally, response-evaluable patients with intermediate-risk NMIBC and FGFR alterations (cohort 3; n = 31) experienced a 12-week complete response (CR) rate of 90%, with 100% of patients experiencing a clinical response. The CR rate was consistent across dose levels and 86% of CRs were ongoing at the data cutoff. The 6-month and 9-month durable response rates were 100% (95% CI, 100%-100%) and 89% (95% CI, 43%-98%), respectively.

“Despite available treatment options for patients with NMIBC, recurrences are high underscoring the need for effective therapies,” Antoni Vilaseca Cabo, MD, adjunct physician of the Urology Service at Hospital Clínic de Barcelona in Spain, said during a presentation of the data. “Activating FGFR alterations are prevalent in [approximately] 50% to 80% of patients with NMIBC and they may function as oncogenic drivers. Erdafitinib is a selective pan-FGFR tyrosine kinase inhibitor approved in the US and other countries to treat patients with advanced or metastatic urothelial carcinoma with susceptible FGFR3 alterations following at least 1 prior systemic treatment. TAR-210 is a novel target-releasing system designed for sustained local delivery of erdafitinib over 3 months in the bladder.”

The first-in-human study of TAR-210 enrolled patients with NMIBC as well as FGFR alterations, and a flexible molecular eligibility strategy was used. Patients in cohort 1 had recurrent high-risk disease that was high-grade Ta/T1, papillary only, with no carcinoma in situ; they had received Bacillus Calmette-Guérin, did not undergo radical cystectomy, and underwent transurethral resection of bladder tumor (TURBT) with complete resection of all visible disease before treatment. In cohort 3, patients had recurrent disease that was intermediate-risk and low-grade Ta/T1; patients had target lesions prior to treatment.

Patients in both cohorts received TAR-210 at a dose of approximately 2 mg/day or approximately 4 mg/day during the dose escalation phase with placement of the device occurring every 3 months. Both dose levels were expanded in part 2, which was the dose expansion phase. Response was assessed every 3 months with treatment continuing up to 1 year if patients were recurrence free in cohort 1 or experienced a CR in cohort 3.

The primary end point was safety. Secondary end points included RFS, duration of CR, and pathological CR rate, among others.²

The baseline characteristics were generally well balanced between cohort 1 and 3 (n = 43); the median age was 73 years (range, 62-90) vs 67 years (range, 41-89), respectively. Most patients in both cohorts were male (71% vs 79%), White (81% vs 60%), had an ECOG performance status of 0 (62% vs 79%), had stage Ta tumors (76% vs 95%), and had FGFR3 mutations (90% vs 95%). The median number of prior tumor ablative procedures and TURBT was 4 (range, 1-12) vs 2 (range, 1-14), respectively.¹

In terms of safety, most adverse effects (AEs) were grade 1 or 2 lower urinary tract events. In the overall safety population (n = 64) most patients experienced at least 1 any-grade AE (84%) and 47% experienced an any-grade treatment-related AE (TRAE). Any-grade TRAEs included hematuria (28%), dysuria (19%), micturition urgency (13%), and urinary tract infection (8%). Twenty-two percent of patients experienced a TRAE of grade 2 severity or higher; no dose-limiting toxicities were reported, 2 patients discontinued treatment due to TRAEs, and 2 patients experienced serious TRAEs of pyelonephritis and sepsis or urinary tract infection and sepsis, respectively.

“TAR-210 provided high erdafitinib concentrations in urine with very low plasma concentrations, limiting systemic toxicities,” Vilaseca Cabo noted.

Additionally, the phase 3 MoonRISe-1 study (NCT06319820) has been initiated in patients with FGFR-altered intermediate-risk NMIBC based on these phase 1 findings.

Editor’s Note: Dr Vilaseca Cabo cited receiving consulting/advisory fees from Accord, Astellas, Bayer, and Janssen, as well as travel support from Astellas, Janssen, and Recordati.

References

1. Vilaseca A, Jayram G, Raventos C, et al. First safety and efficacy results of the TAR-210 erdafitinib intravesical delivery system in patients with non–muscle-invasive bladder cancer with select FGFR alterations. J Urol. Published online May 1, 2024. doi:10.1097/01.JU.0001008712.53259.7d.02
2. Study of erdafitinib intravesical delivery system for localized bladder cancer. ClinicalTrials.gov. Updated April 24, 2024. Accessed May 5, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05316155