SUMMARY

• TAR-200-102 (NCT02720367) was a phase 1b, open-label, prospective, multicenter study that evaluated the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of TAR-200 in 12 patients with intermediaterisk (IR) non-muscle-invasive bladder cancer (NMIBC).^1,2
  • The primary endpoint was safety. Any-grade treatment-emergent adverse events (TEAEs) and TAR-200-related TEAEs were reported in 92% (n=11) and 75% (n=9) of patients, respectively, and were grade ≤2 in severity. The most common TAR-200-related TEAEs included urgency, dysuria, and hematuria.¹
  • TAR-200 was well-tolerated in all patients, with no occurrences of unscheduled removal.¹
  • Overall, 42% (n=5) of patients achieved complete response (CR).¹
  • Plasma gemcitabine concentrations remained below the detection level.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-200-102 Study

van Valenberg et al (2024)¹ evaluated the safety, tolerability, PK, and preliminary efficacy of TAR-200 in patients with IR NMIBC (N=12).

Study Design/Methods

• Phase 1b, open-label, prospective, multicenter study
• Patients received two 7-day (arm 1) or 21-day (arm 2) dosing cycles of TAR-200 over a 4- to 6-week period; see Figure: TAR-200-102 Study Design.
• The primary endpoint was the safety of TAR-200 during the primary study period, defined as the period between the first TAR-200 insertion and post-transurethral resection of bladder tumor (TURBT)/PK visit.
• Safety was evaluated by adverse events (AEs), clinical laboratory tests, vital signs, physical examinations, investigational product events, bladder postvoid residual volume, and cystoscopy findings.

Results

Patient Characteristics

• Overall, 12 patients received TAR-200 in arm 1 (n=11) and arm 2 (n=1). See Table:  Patient Disposition).

• The baseline characteristics are described in Table: Patient Demographics and Baseline Characteristics.

Safety

• The first (12/12) and second (10/12) TAR-200 insertions were successful (defined as TAR-200 appearing undamaged and appropriately configured after insertion by cystoscopy assessment).
• A summary of the most common TEAEs occurring in ≥15% of patients is shown in Table: Most Common TEAEs Occurring in ≥15% of Patients.
  • TEAEs experienced in arm 2 were consistent with arm 1.
• No TAR-200-related grade ≥3 TEAEs or serious AEs were reported. During the surveillance period, 1 serious AE of severe urinary tract infection (UTI) unrelated to TAR-200 occurred.

• Overall, 33% (4/12) of patients reported ≥1 procedure-related TEAE (urinary placement catheter [UPC] and/or cystoscopy), including hematuria (n=3; 25%), penile pain (n=2; 17%), malaise (n=1; 8%), UTI (n=1; 8%), and noninfective cystitis (n=1; 8%).
  • UPC-related TEAEs were reported in 2 patients (mild UTI, n=1; mild hematuria, n=1).
• One investigational procedure event was observed when TAR-200 did not configure as expected due to improper removal.
• No deaths were reported.

Tolerability

• TAR-200 was well-tolerated in all patients, with no occurrence of early removal due to TAR-200-related TEAEs or meeting the predefined safety criteria.
• No patients discontinued due to TEAEs.
• Two patients did not undergo the second dosing cycle of TAR-200 due to TAR-200- and procedure-related TEAEs experienced during the first dosing cycle.
  • One patient had mild hematuria, penile pain, and moderate urinary urgency.
  • Another patient had mild dysuria, urgency, urinary incontinence, and abdominal pain.

PK

• Plasma gemcitabine concentrations remained below the detection level; plasma 2′,2′-difluorodeoxyuridine (dFdU) concentration ranged between 0.101 and 0.163 µg/mL.
• Urine gemcitabine concentrations were detectable after 7 days of instillation, with the maximum mean concentrations observed 3 days after both dosing cycles (range, 18.2-15.7 µg/mL); urine dFdU concentration ranged between 1.48 and 0.36 µg/mL.

Efficacy

• All patients attempted to undergo TURBT, except for 1 patient who did not have any visible tumor where the tumor was initially observed. This patient was considered as achieving CR.
• Of the 12 patients, 5 (42%) achieved CR.
• The remaining patients had Ta (grade 2a, n=3; grade 1, n=1; unknown grade, n=1) and carcinoma in situ (grade 3, n=1).
• During the surveillance period, 9/10 patients ended study participation after a cystoscopy detected suspicious disease.

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.