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). The primary endpoint is overall complete response (CR) rate.^1,2
  • At the clinical data cutoff date of March 31, 2025, 85 patients were treated with INLEXZO monotherapy (cohort 2).¹  
  • The median number of prior BCG doses was 12 (range, 7-42). 
  • The overall centrally assessed CR rate in patients at any time was 82.4% (70/85; 95% confidence interval [CI], 72.6-89.8). The Kaplan-Meier-estimated 12-month CR rate was 45.9% (39/85).¹ 
  • Median follow-up in responders (n=70) and duration of response (DOR) were 20.2 months (range 5-48) and 52.9% (37/70), respectively.¹ 
  • Most treatment-emergent adverse events (TEAEs) were grade 1 or 2 at the time of the analysis. The most common treatment-related adverse events (TRAEs; any grade) are reported in the Table: Most Common TRAEs in the INLEXZO Monotherapy Group (Cohort 2).¹ 

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.

CLINICAL DATA

SunRISe-1 Study

Daneshmand et al (2025)¹ summarized the 1-year results of INLEXZO monotherapy (cohort 2), including use in patients with prior intravesical BCG use. 

Study Design/Methods

• Phase 2b, ongoing, randomized, open-label, parallel-cohort, multicenter study.^1,2 
• Patients in cohort 2 received INLEXZO (indwelling) monotherapy every 3 weeks for the first 24 weeks (6 months) and then every 12 weeks (Q12W) through week 96 (year 2).^1,2 
  • 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.
• Reinduction was not allowed for nonresponders per study protocol.³
• Select inclusion criteria:
  • Age ≥18 years
  • Histologically confirmed diagnosis of persistent or recurrent high-risk NMIBC CIS with or without papillary disease (tumor grade [T]1, high-grade Ta) within 12 months of completion of the last dose of BCG therapy
  • Ineligible for or have elected not to undergo RC
  • BCG-unresponsive HR-NMIBC after treatment with adequate BCG therapy^1,2
    • Adequate BCG therapy 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 criteria²:
  • 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-programmed death 1 (PD-1) agent, anti-programmed death‑ligand 2 (PD‑L2) agent, or agent targeting inhibitory T-cell receptor
• Primary endpoint: Overall complete response (CR) rate at any time^1,2,4
  • Overall CR rate is defined as the percentage of patients achieving a CR at any time posttreatment. CR was defined as ≥1 of the following: (1) negative cystoscopy and negative (including atypical) urine cytology, or (2) positive cystoscopy with biopsy-proven benign or low-grade NMIBC and negative (including atypical) urine cytology.
  • Disease-response assessments based on cystoscopy and central urine cytology Q12W for up to 2 years, then every 24 weeks (Q24W) until end of study; local imaging (computed tomography/magnetic resonance imaging) Q24W until the end of study; and central pathology (bladder biopsy/transurethral resection of bladder tumor) at weeks 24 and 48 in cohorts 1-3 or as clinically indicated in cases of positive cystoscopy
• Key secondary endpoints: Duration of response (DOR), overall survival (OS), safety, tolerability, pharmacokinetics, patient-reported outcomes (PROs)^1,2
• Exploratory endpoint: Time to cystectomy

Results

Patient Characteristics

• The characteristics of patients treated with INLEXZO monotherapy in cohort 2 (n=85) are summarized in Table: Patient Characteristics in the INLEXZO Monotherapy Group (Cohort 2).
• Consistent modality of cystoscopy at baseline and postbaseline were observed in 91.8% of patients.
• White light cystoscopy was the most frequently used modality; 1 patient had blue light cystoscopy at baseline and white light cystoscopy at follow-up.

Efficacy

• At the data cutoff date of March 31, 2025, the overall CR rates in cohort 2 are summarized in Table: CR Rates in the INLEXZO Monotherapy Group (Cohort 2).
• Median time to onset of response was 2.8 months.
• In total, 96% of CRs were achieved during the first disease assessment.
  • The remaining patients who achieved CR were nonevaluable for disease response at week 12 due to missing samples or assessments, but they achieved CR at the subsequent evaluation.

• CR rates across patient subgroups are summarized in Table: CR Rates Across Patient Subgroups in the INLEXZO Monotherapy Group (Cohort 2).

• The DOR rates in cohort 2 are summarized in Table: DOR Rates in the INLEXZO Monotherapy Group (Cohort 2).

• Disease recurrence and progression reported in cohort 2 are summarized in Table: Disease Recurrence and Progression in the INLEXZO Monotherapy Group (Cohort 2).
• Among the 33 patients with centrally assessed disease recurrence or progression, 3 deaths unrelated to treatment were reported.

• In total, 25 patients received subsequent treatment.
  • Of the 85 patients, 18 (21.2%) underwent RC.
  • Of the 70 responders, 12 (17.1%) underwent RC.
• Median time to cystectomy was not estimable.
• The 12- and 24-month RC-free rates were 86.6% (95% CI, 76.6-92.6) and 75.5% (95% CI, 63.4-84.1), respectively.
• The 6- and 12-month OS rates were 98.7% (95% CI, 91.2-99.8) and 94.7% (95% CI, 86.5-98).
  • Total number of deaths in cohort 2 was 7 (8.2%). No deaths were treatment-related.

Safety

• At the data cutoff date of March 31, 2025, most treatment-emergent adverse events (TEAEs) were grade 1 or 2 in severity.
• Median time to AE resolution was 3 weeks (range, 0.1+ to 150.3+).
• No treatment-related deaths were reported.
• The overall safety profile of patients in cohort 2 is summarized in Table: Overall Safety Profile of the INLEXZO Monotherapy Group (Cohort 2).

• The most common any-grade and grade ≥3 TRAEs by preferred term reported in cohort 2 are summarized in Table: Most Common TRAEs in the INLEXZO Monotherapy Group (Cohort 2).

Tolerability

• The INLEXZO insertion success rate was 99% (745/755).³ 

Patient-Reported Outcomes

• At baseline, 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 75.0 (standard deviation [SD], 16.7) and 86.2 (SD, 17.3), respectively.
• Mean GHS and PF scores remained stable on INLEXZO monotherapy treatment, with changes not exceeding the 10-point threshold for clinically meaningful change.

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 19 August 2025.