SUMMARY

• INLEXZO (gemcitabine intravesical system) is an intravesical drug releasing system (iDRS), referred to as TAR-200 in literature.¹ 
• SunRISe-1 (NCT04640623) is an ongoing, phase 2b, open-label, randomized, parallel-cohort, multicenter study evaluating the efficacy and safety of INLEXZO plus systemic cetrelimab (investigational IgG4 antibody targeting PD-1 receptor; cohort 1), INLEXZO monotherapy (cohort 2), or cetrelimab monotherapy (cohort 3) in patients with Bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary disease who are ineligible for or decline radical cystectomy (RC). INLEXZO monotherapy is additionally being studied in patients with BCG-unresponsive papillary-only high-risk NMIBC (no CIS; cohort 4, per protocol amendment).^1-3 
  • As of March 31, 2025, 85 patients were treated with INLEXZO monotherapy (cohort 2).¹ 
  • In cohort 2, any grade and grade ≥3 urinary tract infections (UTIs) occurred in 21.2% (18/85) and 1.2% (1/85) of patients treated with INLEXZO monotherapy.
  • INLEXZO-related UTIs leading to interruption occurred in 4.7% of patients.¹ 
• Daneshmand et al (2025)¹ included the SunRISe-1 study protocol for periprocedural antibiotic use with insertion and removal of INLEXZO and UTI management with INLEXZO use.
• Pradere et al (2025)⁴ summarized the clinical management of side effects, including UTI, associated with iDRSs, such as INLEXZO.

Product Labeling

• INLEXZO (gemcitabine intravesical system) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/INLEXZO-pi.pdf.
• INLEXZO (gemcitabine intravesical system) [Instructions for Use]. Horsham, PA: Janssen Biotech, Inc; https://www.janssenlabels.com/package-insert/product-instructions-for-use/INLEXZO-ifu.pdf.
• Prophylactic antibiotics may be used at the discretion of the treating urologist with each INLEXZO insertion and removal.⁵
• Instruct patients to drink adequate fluids (approximately 1,500 mL per day) during therapy with INLEXZO to ensure adequate urine production for drug release.⁵

CLINICAL DATA

SunRISe-1 Study

The results of the SunRISe-1 study are also included in the INLEXZO product labeling. The incidence of UTIs described below may vary from that in the INLEXZO product labeling due to the difference in evaluation of the individual safety events, contributing to differences in reported percentages.

Daneshmand et al (2025)¹ summarized the 1-year results, including the incidence of UTI with INLEXZO monotherapy in BCG-unresponsive high-risk NMIBC with CIS with or without papillary disease (cohort 2).

Study Design/Methods

• Phase 2b, ongoing, randomized, open-label, parallel-cohort, multicenter study^1-3
• Patients in cohort 2 received INLEXZO (indwelling) monotherapy every 3 weeks for the first 24 weeks (6 months) and then every 12 weeks through week 96 (year 2).^1-3
  • Patients continued treatment with INLEXZO for up to 2 years or until confirmed high-risk disease persistence, recurrence, or progressive disease based on central urine cytology and/or central biopsy assessment or local biopsy/local imaging.¹ 

Results

• As of March 31, 2025, a total of 85 patients were enrolled in the INLEXZO monotherapy group (cohort 2).
• In the INLEXZO monotherapy group (cohort 2), any grade and grade ≥3 UTIs occurred in 21.2% (18/85) and 1.2% (1/85) of patients treated with INLEXZO monotherapy (cohort 2).
• Grade 3 urosepsis occurred in one patient treated with INLEXZO monotherapy (cohort 2).
• INLEXZO-related UTIs leading to interruption occurred in 4.7% of patients. 
  • INLEXZO interruption was defined as when an INLEXZO dose was skipped or INLEXZO was removed early.
  • Most patients had 1-2 skipped INLEXZO doses and resumed treatment.

Management of UTI

• Daneshmand et al (2025)^1,6 included the SunRISe-1 study protocol for periprocedural antibiotic use with insertion and removal of INLEXZO and UTI management with INLEXZO use.
  • To mitigate the risk of UTIs, patients received at least 1 dose of prophylactic periprocedural antibiotics for INLEXZO insertion or removal. Antibiotics for standard cystoscopy and TURBT were administered in accordance with standard of care.⁶
  • INLEXZO was removed and INLEXZO dosing was delayed if a grade ≥2 active UTI occurred that the investigator believed to be clinically significant.⁶ 
• Note these interventions from the SunRISe-1 study may not reflect current practice. Interventions should be based on patient presentation and the clinical judgment of the treating physician.

Pradere et al (2025)⁴ summarized clinical management recommendations from a panel of urologists and oncologists with experience in iDRS clinical trials (SunRISe and MoonRISe).

General Principles and Prophylactic Measures

The general recommendations for the management of iDRS-associated side effects include the following:

• Counsel patients prior to and during the treatment course on potential LUTS and their management. Assessing for preexisting LUTS before treatment initiation, particularly in males with storage symptoms per International Prostate Symptom Score, is crucial as these may worsen with iDRS treatment.⁴
• Instruct patients to consume at least 1500 mL (approximately 6.5 cups) of nonalcoholic, noncaffeinated liquids daily during the iDRS dosing period to promote adequate urine production.⁴
• Patients with ongoing LUTS or a history of LUTS prior to treatment should be advised to avoid bladder irritants (eg, spicy foods, caffeine, citrus fruits). If LUTS occur, urinalysis and urine culture should be conducted, and, if UTI is present, treatment should be as per the standard practice.⁴

The recommendations for iDRS toxicity management are shown in the figure: Flowchart of Expert Panel Recommendations for iDRS Toxicity Management

• Recommendations for the management of UTI following iDRS treatment are summarized in the table: Expert Recommendations for the Management of UTI and Bacteriuria.
• The first step in the management of UTI in patients receiving iDRS treatment is the initiation of antibiotics that are selected based on urinalysis and urine culture results.⁴

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 14 October 2025.

Summarized in this response are relevant data limited to INLEXZO monotherapy (cohort 2) of the phase 2b SunRISe-1 study in patients with BCG-unresponsive high-risk NMIBC with CIS with or without papillary tumors.