2. UroToday Home
  3. Conference Highlights
  4. ESMO 2023
  5. ESMO 2023 Bladder Cancer

ESMO 2023

ESMO 2023: TAR-210 Erdafitinib Intravesical Delivery System in Patients with Non–Muscle-Invasive Bladder Cancer with Select FGFR Alterations: First Safety and Efficacy Results

(UroToday.com) The 2023 European Society of Medical Oncology (ESMO) Annual Congress held in Madrid, Spain between October 20th and 24th, 2023 was host to a non-prostate, genitourinary tumors mini oral session. Dr. Antoni Vilaseca presented the first safety and efficacy results of the TAR-210 erdafitinib intravesical delivery system in patients with non–muscle-invasive bladder cancer (NMIBC) with select Fibroblast Growth Factor Receptor (FGFR) alterations.


Treatment options remain limited for patients with recurrent NMIBC. FGFR alterations are prevalent in 50 – 80% of NMIBCs and may function as oncogenic drivers.1,2 Erdafitinib is an oral pan-FGFR tyrosine kinase inhibitor approved in the United States and 18 other countries to treat FGFR-altered advanced or metastatic urothelial carcinoma after progression on platinum-containing chemotherapy. Oral erdafitinib has shown activity in both intermediate- and high-risk NIMBC populations.3

TAR-210 is a novel drug delivery system designed to provide locally targeted therapy for patients with bladder cancer. It is inserted into the bladder through a dedicated urinary placement catheter and removed via cystoscopy. It allows for the sustained release of erdafitinib for 3 months while limiting systemic toxicities.

This is an open label, multicenter, phase 1 trial that aims to evaluate the safety, pharmacokinetics, and efficacy of TAR-210. This study included 2 cohorts:

  • Cohort 1; High-risk NMIBC (HG Ta/T1, no CIS, papillary only), BCG-experienced/unresponsive and not undergoing radical cystectomy. All patients in this cohort had a TURBT with complete resection of all visible disease prior to treatment
  • Cohort 3: Intermediate-risk NMIBC (LG Ta/T1 disease) and visible target lesions prior to treatment (chemoablation design)

Part 1 was a dose escalation phase with two different erdafitinib release rates being evaluated. Part 2 was the dose expansion phase for patients in Cohorts 1 and 3. Response was assessed every 3 months with continued treatment for up to 1 year if recurrence-free (Cohort 1) or until complete response (Cohort 3). Of note, the first response assessment was at 3 months.TAR 210 flow
For patients in Cohort 1 (n=16), the median age was 73.5 years, 75% were male, 75% and 25% had tumor stage Ta and T1, respectively, 44% had multiple tumors, and 100% had prior BCG. In 11 patients with an available response assessment, 9 (82%) were recurrence-free. The median recurrence-free survival has not been reached yet (95% CI: 2.96 months – not reached). The median duration of treatment exposure was 3.7 – 4.3 months.TAR 210 duration
In the chemoablative Cohort 3 (n=27), the median age was 67 years, 85% were male, 100% had tumor stage Ta, 41% had multiple tumors, 59% had prior intravesical therapy, and 22% had prior BCG. In 15 patients with available response assessment, 13 (87%) achieved a complete response. All complete responses were ongoing as of data collection cut-off (median duration of response not reached yet). The median duration of treatment exposure was 3.3 – 4.2 months.TAR 210 fgfr altered ir nmibc
From a pharmacokinetics standpoint, TAR-210 provided sustained erdafitinib release in urine over 90 days with very low plasma concentrations. The steady state mean plasma concentrations were more than 50-fold lower than with oral erdafitinib 9 mg daily. No cases of hyperphosphatemia were observed.TAR 210 cycle
From a safety standpoint, there were no dose-limiting toxicities. Overall, common treatment-related adverse events were grade 1 – 2 lower urinary tract events. 2 patients discontinued treatment due to adverse events of low-grade urinary symptoms. 1 patient had a serious adverse event and sepsis unrelated to TAR-210. No deaths have been reported.TAR 210 trae
Dr. Vilaseca concluded as follows:

  • TAR-210 is a novel intravesical drug delivery system providing local, sustained release of erdafitinib in the bladder over 90 days with minimal systemic exposure
  • TAR-210 shows promising clinical activity in patients with FGFR-altered high-risk and intermediate-risk NMIBC
    • 82% of patients with BCG-experienced high-risk NMIBC in Cohort 1 are recurrence-free
    • 87% of patients with intermediate-risk NMIBC in Cohort 3 achieved a complete response
  • TAR-210 was well tolerated with limited systemic toxicity
    • TAR-210-related grade ≥2 adverse events and discontinuations were infrequent, with predominantly grade 1 urinary system adverse events
  • These encouraging preliminary results support phase 3 studies of TAR-210 in FGFR-altered localized bladder cancer

Presented by: Antoni Vilaseca, MD, Associate Medical Professor at the Universitat de Barcelona, Barcelona, Spain 

Written by: Rashid K. Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 European Society of Medical Oncology (ESMO) Annual Congress held in Madrid, Spain between October 20th and 24th, 2023

References:
  1. Hernandez S, Lopez-Knowles E, Lloreta J, et al. Prospective study of FGFR3 mutations as a prognostic factor in nonmuscle invasive urothelial bladder carcinomas. J Clin Oncol. 2006;24(22):3664-71.
  2. Knowles MA, Hurst CD. Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity. Nat Rev Cancer. 2015;15(1):25-41.
  3. Daneshmand S, Zaucha R, Gartrell BA, et al. Phase 2 study of the efficacy and safety of erdafitinib in patients (pts) with intermediate-risk non–muscle-invasive bladder cancer (IR-NMIBC) with FGFR3/2 alterations (alt) in THOR-2: Cohort 3 interim analysis. J Clin Oncol. 2023;41(Suppl 6):504.