Product labeling

• INLEXZO (gemcitabine intravesical system) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc; https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/INLEXZO-pi.pdf.
• INLEXZO (gemcitabine intravesical system) [Instructions for Use]. Horsham, PA: Janssen Biotech, Inc; https://www.jnjlabels.com/package-insert/product-instructions-for-use/INLEXZO-ifu.pdf.

CLINICAL DATA

SunRISe-1 Study

SunRISe-1 (NCT04640623) is an ongoing, phase 2b, open-label, randomized, parallel-cohort, multicenter study evaluating the efficacy and safety of INLEXZO (gemcitabine intravesical system), an intravesical drug releasing system (iDRS), referred to as TAR-200 in literature.^1-3

The SunRISe-1 study is assessing INLEXZO plus cetrelimab (investigational immunoglobulin G4 [IgG4] antibody targeting programmed cell death protein-1 [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).^1-3

Daneshmand et al (2025)¹ summarized the 1-year results of the SunRISe-1 study, including INLEXZO monotherapy in patients with BCG-unresponsive high-risk NMIBC with papillary-only disease (cohort 4).

Study Design/Methods

• Phase 2b, ongoing, randomized, open-label, parallel-cohort, multicenter study^1,3
  • Patients were enrolled between March 2021 and April 2024 at 142 sites in 14 countries.¹
  • Three CIS cohorts were originally designed to enroll 200 patients randomized 2:1:1 to cohorts 1-3.¹
  • In June 2023, INLEXZO monotherapy development was prioritized in the CIS population, and enrollment in cohorts 1 and 3 was closed on the basis of the more favorable risk-benefit profile observed with INLEXZO monotherapy in this setting based on the totality of evidence.¹
  • The protocol was amended to expand the INLEXZO monotherapy cohort to add an additional cohort of 80 patients for INLEXZO monotherapy in patients with papillary-only high-risk NMIBC (cohort 4).¹
  • Reinduction was not allowed for nonresponders per study protocol.⁵ 
• Patients in cohort 4 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
• Select inclusion criteria:
  • Age ≥18 years
  • Histologically confirmed diagnosis of persistent or recurrent high-risk NMIBC papillary disease only (any T1, high-grade tumor [T]a) without CIS within 12 months of completion of the last dose of BCG therapy
  • Negative or atypical local urine cytology at screening (for High-Grade Urothelial Carcinoma [HGUC])³
  • Ineligible for or have elected not to undergo RC
  • BCG-unresponsive high-risk NMIBC after treatment with adequate BCG therapy³
    • Adequate BCG therapy is defined as a minimum of 5 of 6 full doses of an induction course (adequate induction) plus 2 of 3 doses of a maintenance course, or ≥2 of 6 doses of a second induction course
  • Eastern Cooperative Oncology Group performance status of 0-2
• Select exclusion criteria³:
  • Muscle-invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (UC)
  • UC or histological variant at any site outside of the urinary bladder
  • Prior therapy with anti-PD-1 agent, anti-programmed death‑ligand 2 (PD‑L2) agent, or agent targeting co-inhibitory T-cell receptor
• Primary endpoint: Disease-free survival (DFS) rate
  • DFS is defined as the time from the first dose of treatment to high-risk disease recurrence (high-grade Ta, any T1, or CIS), progression (progression to muscle-invasive bladder cancer [muscle-invasive bladder cancer (MIBC); T≥2], lymph node [N+] or distant disease [M+]), or death due to any reason)²
• Key secondary endpoints: Overall survival (OS), safety, tolerability, pharmacokinetics (PK), and patient-reported outcomes (PROs)^1-3

Results

Patient Characteristics

• The characteristics of patients treated with INLEXZO monotherapy in cohort 4 (n=52) are summarized in Table: Patient Characteristics in the INLEXZO Monotherapy Group (Cohort 4).

Efficacy

Primary Endpoint - DFS Rates

• The DFS rates in cohort 4 are summarized in Table: DFS Rates in the INLEXZO Monotherapy Group (Cohort 4).
• At the data cutoff date of March 31, 2025, the median follow-up was 12.8 months (range, 4-17) and the median DFS was not estimable (NE).¹
• At the data cutoff date of July 03, 2025, the median follow-up was 15.9 months (range, 4-20) and the median DFS was NE.⁴

• At the data cutoff date of March 31, 2025, there were 5.8% (3/52) patients who had RC.⁵
• At the data cutoff date of July 03, 2025, there were 7.7% (4/52) patients who had RC.⁴ 
  • The 12- and 18-month RC-free rates were 93.8% (95% CI, 81.9-97.9) and 91.0% (95% CI, 77.5-96.6), respectively.

Secondary Endpoints - Progression-Free Survival and OS

• NMIBC recurrence or progression occurred in 21.2% (11/52) of patients.^1,5
  • Progression to MIBC was reported in 1.9% (1/52) of patients.⁵
  • Progression is defined as advancing to MIBC (T≥2), lymph node (N+), or distant disease (M+), or death due to any cause.
• Median progression-free survival (PFS) and OS were NE.^4,5
  • The 9-month PFS rate was 95.6% (95% confidence interval [CI], 83.5-98.9); n=32 (at risk).⁵
  • The 12-month PFS rate was 95.6% (95% CI, 83.5-98.9); n=27 (at risk).⁴ 
  • The 9-month OS rate was 98.0% (95% CI, 86.4-99.7); n=46 (at risk).⁵
  • The 12-month OS rate was 98.0% (95% CI, 86.6-99.7); n=41 (at risk).⁴ 
• Deaths unrelated to the treatment occurred in 3.8% (2/52) of patients due to acute renal failure and congestive cardiac failure.^1,2

Safety

• At the data cutoff date of March 31, 2025, the overall safety profile of patients in cohort 4 is summarized in Table: Overall Safety Profile of the INLEXZO Monotherapy Group (Cohort 4) - Data Cutoff Date of March 31, 2025.
  • No treatment-related deaths were reported.¹

• At the data cutoff date of July 03, 2025⁴:
  • Most treatment-emergent adverse events were grade 1 or 2 with a median resolution time of 3.3 weeks.
  • Any grade and grade ≥3 treatment-related adverse events (TRAEs) were reported in 80.8% (42/52) and 13.5% (7/52) patients, respectively.
  • Serious TRAEs occurred in 5.8% patients (n=3), due to sepsis, urinary tract infection (UTI), and spinal fracture (n=1 each).
  • Treatment was discontinued due to TRAEs in 7.7% patients (n=4), due to micturition urgency (n=4), pollakiuria (n=2), dysuria (n=2), and bladder spasm, urinary incontinence, and UTI (n=1 each).
  • No treatment-related deaths were reported.
• The most frequent any-grade and grade ≥3 TRAEs in cohort 4 are summarized in Table: Most Frequent TRAEs in the INLEXZO Monotherapy Group (Cohort 4).

Tolerability

• At the data cutoff date of March 31, 2025, the INLEXZO insertion success rate was 99.5% (387/389).⁵
• At the data cutoff of July 03, 2025, the INLEXZO insertion success rate was 99.8% (419/420).⁴ 

Patient-Reported Outcomes

• At baseline, the mean global health status (GHS) and physical functioning (PF) scores on the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) were 77.1 (standard deviation [SD], 18.7) and 85.4 (SD, 16.8), respectively.⁴ 
• Least squares mean GHS and PF scores remained stable on INLEXZO monotherapy treatment, with changes not exceeding the 10-point threshold for a clinically meaningful change.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 11 December 2025.