SUMMARY

• TAR-200-101 (NCT02722538) was a phase 1b, open-label, multicenter study that evaluated the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of neoadjuvant TAR-200 in 23 patients with muscle invasive bladder cancer (MIBC) before radical cystectomy (RC).^1,2
  • Safety was the primary endpoint of the study. Treatment-emergent adverse events (TEAEs) occurred in 10 patients and were mostly grade 1 or 2 (n=9). The most common TEAEs related to TAR-200 in the intention-to-treat (ITT) population were pollakiuria (n=3) and urinary incontinence (n=2).¹
  • Pathologic response was achieved in 10 patients who underwent pathology at RC:
    4 achieved complete response (CR) and 6 achieved partial response (PR). In arm 1 (ie, those with residual tumor >3 cm after transurethral resection of bladder tumor [TURBT]), 4 of 10 patients achieved pathologic downstaging (CR, n=1; PR, n=3). In arm 2 (ie, those who had undergone maximal TURBT [residual tumor <3 cm]), 6 of 10 patients achieved pathologic downstaging (CR, n=3; PR, n=3).¹

BACKGROUND

• TAR-200 (JNJ-17000139) is an investigational intravesical system that is designed to provide local release of gemcitabine in the bladder. TAR-200 contains gemcitabine and urea mini tablets within a dual-lumen silicone tube for gradual release of gemcitabine by an osmotic delivery mechanism throughout the prescribed indwelling period.^1,3-6
• TAR-200 is inserted intravesically via urinary placement catheter, after which it self-coils into a bi-oval shape. Removal of TAR-200 can be achieved using grasping forceps and flexible cystoscopy.^4,6 

CLINICAL DATA

TAR-200-101 Study

Daneshmand et al (2022)¹ evaluated the safety, tolerability, PK, and preliminary efficacy of neoadjuvant TAR-200 in patients with MIBC before RC (N=23).

Study Design/Methods

• Phase 1b, open-label, multicenter study^1,2
• Patients were serially enrolled in 2 study arms; arm 1 consisted of patients with residual tumor >3 cm after TURBT and arm 2 consisted of patients with residual tumor <3 cm after TURBT.
• Patients in both arms received two 7-day dosing cycles of TAR-200 with a 14-day resting period in between cycles, before undergoing RC; see Figure: TAR-200-101 Study Design.

Results

Patient Characteristics

• Overall, 23 patients were enrolled and constituted the ITT population.
• The baseline demographics and disease characteristics are described in Table: Select Patient Baseline Characteristics.

Safety

• Of the 23 patients in the ITT population, 22 completed cycle 1 of TAR-200 insertion and removal, and 20 completed both dosing cycles.
• All patients with successful insertion of TAR-200 were considered tolerant to TAR-200; no patient experienced adverse events (AEs) that led to early removal of TAR-200.
• A summary of TAR-200- or procedure-related TEAEs is shown in Table: TAR-200- or Procedure-Related TEAEs^a in the ITT Population (Both Arms Combined; N=23).
• Overall, TEAEs (related or nonrelated) occurred in 10 patients after the first insertion of TAR-200 through the day of RC (arm 1, n=4; arm 2, n=6).
• TEAEs were mostly grade 1 or 2 (n=9) except 1 grade 3 non-treatment-related TEAE in arm 2 (severe lower abdominal pain occurring with concomitant disease progression). No grade 4 or 5 TEAEs were reported.

Urine and Plasma Concentrations of Gemcitabine and 2’,2’-difluorodeoxyuridine (dFdU)

• During the first dosing cycle, on study day 3, the mean urinary gemcitabine and urine dFdU concentrations were 18.5 and 6.7 µg/mL, respectively, and on study day 7, the concentrations were 6.6 and 2.3 µg/mL, respectively.
• During the second dosing cycle, on study day 24, the mean urinary gemcitabine and urine dFdU concentrations were 15.0 and 4.4 µg/mL, respectively, and on study day 28, the concentrations were 7.8 and 2.7 µg/mL, respectively.
• Plasma gemcitabine concentrations were undetectable in any of the collected samples at any time point.

Efficacy

• The time from TURBT to RC was 28 and 42 days for patients in arm 1 and arm 2, respectively. The median time from the first insertion to RC was 39 days.
• Efficacy outcomes are described in Table: Efficacy Outcomes in the ITT Population.

LiTerature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 23 January 2025.