J&J Medical Connect
INLEXZO™

(gemcitabine intravesical system)

J&J Medical Connect

Connect with us

  • Products

This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

INLEXZO™ (gemcitabine intravesical system)
Medical Information

INLEXZO - Publication Summary: Daneshmand et al (2026) - Matching-adjusted Indirect Comparison Study of INLEXZO vs Novel Agents

Last Updated: 06/29/2026

SUMMARY

  • INLEXZO (gemcitabine intravesical system) is an intravesical drug releasing system (iDRS), referred to as gem-iDRS and TAR-200 in literature.1 
  • Daneshmand et al (2026)2 conducted a matching-adjusted indirect comparison (MAIC) study to compare the relative treatment effect of INLEXZO vs United States Food and Drug Administration (FDA)-approved novel agents (pembrolizumab, nadofaragene firadenovec-vncg [nadofarogene], and nogapendekinalfa inbakicept-pmlnin combination with BCG [NAI + BCG]) in Bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC) for patients from SunRISe-1 study with carcinoma in situ (CIS) ± papillary disease (Cohort 2) and papillary-only disease (Cohort 4). In patients with CIS ± papillary disease (Cohort 2), INLEXZO complete response (CR) rates at any time, at first disease assessment, and at 12 months were assessed against all other novel agents, NAI + BCG, and pembrolizumab and nadofarogene, respectively. For the relative treatment effect comparison for patients with papillary-only disease (Cohort 4), INLEXZO disease-free survival (DFS) rate at 12 months and overall DFS were assessed against pembrolizumab.
    • In patients with CIS ± papillary disease (Cohort 2), INLEXZO provided a statistically significantly higher adjusted CR rate at any time compared to all 3 FDA-approved novel agents (absolute rate difference: vs pembrolizumab, 47% [95% confidence interval [CI], 34%-61%]; vs nadofarogene, 32% [95% CI, 19%-45%]; vs NAI + BCG, 21% [95% CI, 7%-35%]; P<0.05 for all comparisons).
    • An additional analysis showed the impact of reinduction on CR rate. INLEXZO had a significantly higher CR rate at the first disease assessment vs NAI + BCG (absolute rate difference, 36% [95% CI, 22%-51%], P<0.001), based on calculated data that excluded patients who received a second induction.
    • In patients with papillary-only disease (Cohort 4), INLEXZO significantly improved DFS versus pembrolizumab, with a 64% risk reduction (adjusted hazard ratio [HR], 0.36 [95% CI, 0.20-0.64) and a higher 12‑month DFS (adjusted rate, 29% [11.6%-46.2%]).
    • Limitations included that the MAIC methodology can only adjust for baseline characteristics that were observed and reported. Any confounders not consistently reported or missing across studies may affect internal validity. Differences in study designs and outcomes can introduce biases that cannot be fully addressed by MAICs.

Product labeling

BACKGROUND

  • INLEXZO is designed to provide local release of gemcitabine in the bladder. INLEXZO contains gemcitabine and urea mini tablets within a dual-lumen silicone tube for sustained release of gemcitabine by an osmotic delivery mechanism throughout the prescribed indwelling period.1,3-6
  • INLEXZO is inserted intravesically via a urinary catheter, after which it self-coils into a bi-oval shape (see Figure: INLEXZO iDRS). Removal of INLEXZO can be achieved by using grasping forceps and cystoscopy.5,7
  • INLEXZO monotherapy (Cohort 2) is being studied in the phase 2b SunRISe-1 study for patients with BCG-unresponsive high risk NMIBC with CIS, with or without papillary tumors, who have refused or are ineligible for radical cystectomy.8

INLEXZO iDRS3,9,10

A graphic design of a train track AI-generated content may be incorrect.

Matching-adjusted Indirect Comparison STUDy

Daneshmand et al (2026)2 conducted a MAIC study to compare the CR rates (at any time, at first disease assessment, and at 12 months) and DFS rate (overall and at 12 months) of INLEXZO vs FDA-approved novel agents in BCG-unresponsive high-risk NMIBC in patients with CIS ± papillary disease (Cohort 2) and papillary-only disease (Cohort 4), respectively.

Study Design/Methods

  • A systematic literature review was performed to identify novel agents in the BCG-unresponsive high-risk NMIBC setting, which included pembrolizumab (KEYNOTE-057), nadofaragene (CS-003), NAI+BCG (QUILT 3.032) and cretostimogene grenadenorepvec (cretostimogene) (BOND-003). Cretostimogene was excluded from this analysis since it was not FDA approved at the time of the analysis and US prescribing information (USPI) was not available.
  • Primary data source for the MAIC analyses was the patient-level data for INLEXZO monotherapy from SunRISe-1 study in Cohorts 2 and 4, and comparator data from the USPI’s and primary publications of KEYNOTE-057, CS-003, and QUILT 3.032.
  • Study and patient characteristics, patient eligibility criteria, outcome definitions, and reporting timing for SunRISe-1 and trials of FDA-approved novel agents (pembrolizumab [KEYNOTE-057], nadofaragene [CS-003], and NAI+BCG [QUILT 3.032]) were evaluated to assess the feasibility of conducting a MAIC.
  • Three unanchored MAICs for the CIS cohort and two MAIC for the papillary-only cohort were conducted using individual patient data (IPD) from SunRISe-1 Cohorts 2 and 4, respectively.2,11
  • Adjustment of imbalances in patient characteristics (tumor stage, prior doses of BCG instillation, Eastern Cooperative Oncology Group, age, gender and race) was done by weighting the INLEXZO IPD to match the reported baseline characteristics of the comparator trials.2,11
  • The endpoints of interest for the MAIC analyses for SunRISe-1 Cohort 2 were CR rate at any time, CR rate at first disease assessment, and CR rate at 12 months.
    • CR rate was defined as the percentage of patients achieving a CR at any time, at first disease assessment, or at 12 months from the first dose.
    • CR rate at any time was compared between INLEXZO vs all three other novel agents.
    • CR rate at first disease assessment was compared between INLEXZO vs NAI+BCG to remove the impact of reinduction on CR rate, given that reinduction was allowed in patients who did not achieve a CR at month 3 in QUILT 3.032.
    • CR rate at 12 months was compared between INLEXZO vs pembrolizumab and nadofarogene. A similar analysis was not feasible vs NAI+BCG, owing to differences in the duration of response for the patients who underwent re-induction of NAI+BCG.
  • The endpoint of interest for the MAIC analyses for SunRISe-1 Cohort 4 was overall DFS and DFS at 12 months.
    • DFS was compared between INLEXZO (SunRISe-1 Cohort 4) vs pembrolizumab (KEYNOTE-057 Cohort B).
      • There was not sufficient power to test the difference between papillary cohorts for SunRISe-1 and CS-003 due to the small sample size of both cohorts.
      • QUILT 3.032 did not report the number of patients at risk in the published Kaplan-Meier curve for the papillary-only cohort.
  • Limitations included that the MAIC methodology can only adjust for baseline characteristics that were observed and reported. Any confounders not consistently reported or missing across studies may affect internal validity. Differences in study designs and outcomes can introduce biases that cannot be fully addressed by MAICs.

Results

The results of the SunRISe-1 study for BCG-unresponsive high-risk NMIBC with CIS, with or without papillary tumors (Cohort 2) are also included in the INLEXZO product labeling. The efficacy results below may vary from those in the INLEXZO product labeling due to the evaluation of different patient populations in the efficacy analyses, contributing to differences in reported n-values and percentages.


Comparison of Treatment Characteristics and CR Definitions Among Trials Investigating Novel Agents for the Treatment of BCG-Unresponsive High-risk NMIBC With CIS±Papillary Disease or Papillary-only Disease11
Product
INLEXZO
Pembrolizumab
Nadofaragene
NAI + BCG
Trial
SunRISe-1 (Cohort 2)a
KEYNOTE-057b,c
CS-003d,e
QUILT 3.032f,g
Mode of delivery
Intravesical drug releasing system
IV infusion
Intravesical instillation
Intravesical instillation
Dosing regimen
Every 3 weeks for the first 6 months, then every 12 weeks for up to 2 years
200 mg every 3 weeks or 400 mg every 6 weeks for up to 2 years
  • Total 4 doses: 1 induction dose followed by dosing every 3 months for 12 months
  • Patients can continue receiving treatment once every 3 months at the treating physician’s discretion
  • Induction: weekly for 6 consecutive weeks; if CR is not achieved at month 3, then a second induction may be administered
  • Maintenance: weekly for 3 weeks; administration of a maintenance dose at months 4, 7, 10, 13, and 19 for patients with stable disease
  • Additional maintenance may be administered (weekly for 3 weeks at months 25, 31, and 37) to patients with an ongoing CR at month 25 and later
Total number of doses
14 doses over 2 years
16 or 34 doses over 2 years
  • 4 doses in year 1
  • Treat to progression thereafter (4 doses/year)
  • 21-24 doses over 2 years
  • 9 additional doses (optional year 3)
Key inclusion
Adult with BCG-unresponsive HR NMIBC CIS ± papillary disease
Key exclusion
Prior therapy with an anti-PD-1, anti-PD-L2 agent, or with an agent directed to another co-inhibitory T-cell receptor
Prior therapy with an anti-PD-1, anti-PD-L2 agent, or with an agent directed to another co-inhibitory T-cell receptor
Patients with life expectancy <2 years, patients with prior treatment with adenovirus-based drugs and hypersensitivity to IFN alfa2b
Patients with life expectancy <2 years and history of uncontrollable CNS disease
Definition of CR
Negative cystoscopy and negative (including atypical) centrally read UC, or positive cystoscopy with biopsy-proven benign or low-grade NMIBC and negative (including atypical) centrally read UC at any time, and biopsy at weeks 24 and 48
Absence of low-grade Ta, HR disease, and progressive disease (central review) by negative results for cystoscopy (with TURBT/biopsies, as applicable), UC, and computed tomography urography imaging
Negative results for cystoscopy (with TURBT/biopsies, as applicable) and UC
Negative results for cystoscopy (with TURBT/biopsies, as applicable) and UC based on investigator assessment of UC, cystoscopy, and local pathology results
CR at first disease assessment
Percentage of patients achieving CR at first disease assessment following treatment initiation
NA
NA
Percentage of patients achieving CR at first disease assessment following treatment initiation
CR at 12 months
Percentage of patients achieving CR at 12 months from treatment initiation
Percentage of patients achieving CR at 12 months from treatment initiation
Percentage of patients achieving CR at 12 months from treatment initiation
Percentage of patients achieving CR at 12 months from treatment initiation
Timing of CR assessment
Every 12 weeks through week 99 (year 2) and then every 24 weeks thereafter through year 3
Every 12 weeks for 2 years and then every 24 weeks for 3 years
3, 6, 9, and 12 months
Every 3 months for up to 2 years
Key inclusion
Adult with BCG-unresponsive HR NMIBC papillary disease (high-grade Ta, any T1)
Key exclusion
Prior therapy with an anti-PD-1, anti-PD-L2 agent, or with an agent directed to another co-inhibitory T-cell receptor
Prior therapy with an anti-PD-1, anti-PD-L2 agent, or with an agent directed to another co-inhibitory T-cell receptor
Patients with life expectancy <2 years, patients with prior treatment with adenovirus-based drugs and hypersensitivity to IFN alfa2b
Patients with life expectancy <2 years and history of uncontrollable CNS disease
DFS/RFS definition
DFS was defined as the time from first dose of study treatment to the occurrence of one of the following events, whichever occurs first:
Recurrence of HR disease (high-grade Ta, any T1, or CIS)
Progression (an increase in stage from Ta to T1, or to MIBC [T≥2], N+, or M+)
Death from any cause.
DFS of HR NMIBC was defined as the time from first dose to the first occurrence of HR NMIBC or worse (per central pathology/radiology review). The 12‑month DFS rate is the proportion of patients without HR NMIBC or worse at 12 months.
RFS was defined as the time from first dose to the first recurrence of highgrade disease (including progression to MIBC or death). Patients without recurrence were censored at the last assessment without highgrade disease.
DFS was defined as the time from first instillation of BCG + NAI to the absence of HR  disease, with events including highgrade Ta (excluding lowgrade Ta), any T1, persistent or new CIS, disease progression, cystectomy, escalation of therapy, or death.
K-M figure reported
K-M graph reported, patients at risk (n=52)a
K-M graph reported, patients at risk (n=132)h
K-M graph reported, patients at risk (n=48)i
K-M data reported in table, no patient at risk data reported (n=72)g
Abbreviations: BCG, Bacillus Calmette-Guérin; CIS, carcinoma in situ; CNS, central nervous system; CR, complete response; DFS, disease-free survival; HR, high-risk; IFN, interferon; IV, intravenous; K-M, Kaplan-Meier; L2, ligand 2; MIBC, muscle-invasive bladder cancer; NA, not applicable; nadofaragene, nadofaragene firadenovec-vncg; NAI + BCG, nogapendekin alfa inbakicept-pmln in combination with Bacillus Calmette-Guérin; NMIBC, non-muscle invasive bladder cancer; PD-1, programmed-cell death 1; RFS, remission free survival; Ta, noninvasive papillary carcinoma; TURBT, transurethral resection of bladder tumor; UC, urine cytology.aDaneshmand, et al. J Clin Oncol. 2025;43(33):3578-3588.bKeytruda. Prescribing information. Merck & Co., Inc; 2014.cBalar AV, et al. Lancet Oncol. Jul 2021;22(7):919-930.dAdstiladrin. Prescribing information.2024.eBoorjian SA, et al. Lancet Oncol. Jan 2021;22(1):107-117.fAnktiva. Prescribing information. ImmunityBio Inc.; 2024.gChamie K, et al. NEJM Evidence. 2022;2(1).hNecchi A, et al. Lancet Oncol. 2024;25(6):720-30.iNarayan, et al. J Urol. 2024;212(1):74-86.
Patient Characteristics

Baseline Characteristics of Patients in Trials Investigating Novel Agents for the Treatment of BCG-unresponsive High-risk NMIBC, by Disease Cohort2 
Variable
SunRISe-1
INLEXZO
KEYNOTE-057
Pembrolizumab
CS-003
Nadofaragene
QUILT 3.032
NAI + BCG
Cohort 2 (CIS ± Papillary)
n=85
Cohort 4 (Papillary Only)
n=52
CIS ± Papillary
n=96
Papillary Only
n=132
CIS ± Papillary
n=98
Papillary Only
n=48
CIS ± Papillary
n=77
Papillary Only
n=72
Age (years), median (range)
71
(40-88)
71
(42-88)
73
(44-92)
72
(37-87)
70
(44-89)
71
(64-78)
73
(50-91)
72
(NR)
Gender (%)
   Male
80
71
84
79
88
68
86
74
   Female
20
30
16
21
12
32
14
26
Race (%)
   White
87
87
67
66
92
94
90
NR
   Non-White
13
14
33
34
8
6
10
NR
ECOG (%)
   0
92
94
73
77
90
86
83
77
   1+
8
6
27
23
10
14
17
23
Number of prior BCG instillation, median
12
12
12
10
12
NR
12
12
Tumor Stage (%)
  CIS + T1
11
T1: 60
13
T1: 43
5
T1: 30
10
T1: 45
  CIS + Ta
22
Ta: 40
25
Ta: 57
19
Ta: 70
21
Ta: 43
  CIS alone
67.1
NA
63
NA
76
NA
69
NA
Abbreviations: BCG, Bacillus Calmette-Guérin; CIS, carcinoma in situ; ECOG, Eastern Cooperative Oncology Group; NA, not applicable; nadofaragene, nadofaragene firadenovec-vncg; NAI+BCG, nogapendekin alfa inbakicept-pmln in combination with BCG; NMIBC, non-muscle invasive bladder cancer; NR, not reported; T1, tumor invades the subepithelial connective tissue; Ta, noninvasive papillary carcinoma.
MAIC in BCG-unresponsive High-risk NMIBC With CIS ± Papillary Disease (Cohort 2)

MAIC of INLEXZO vs. Novel Agents in the BCG-unresponsive High-risk NMIBC with CIS2 
Comparison
INLEXZO
CR (%)
Comparator
CR (%)
Adjusted Absolute Differencea
Unadjusted Absolute Difference (95% CI)
% (95% CI)
P value
INLEXZO vs Pembrolizumab
88
41
47 (34-61)
<0.001
41 (28-54)
INLEXZO vs Nadofaragene
83
51
32 (19-45)
<0.001
NR
INLEXZO vs NAI + BCG
83
62
21 (7-35)
0.003
NR
Abbreviations: BCG, Bacillus Calmette-Guérin; CI, confidence interval; CIS, carcinoma in situ; CR, complete response; MAIC, matching-adjusted indirect comparisons; nadofaragene, nadofaragene firadenovec-vncg; NAI+BCG, nogapendekin alfa inbakicept-pmln in combination with BCG; NMIBC, nonmuscle-invasive bladder cancer; NR, not reported.aRate difference has been rounded.

MAIC of INLEXZO vs. Novel Agents in BCG-unresponsive High-risk NMIBC with CIS: 12month CR rate2
Comparison
Adjusted Absolute Difference (95% CI)
Unadjusted Absolute Difference (95% CI)
INLEXZO vs Pembrolizumab
26 (7-44)
27 (14-40)
INLEXZO vs Nadofaragene
20 (5-35)
20 (7-34)
INLEXZO vs NAI + BCG
Not feasiblea
Not feasiblea
Abbreviations: BCG, Bacillus Calmette-Guérin; CI, confidence interval; CIS, carcinoma in situ; CR, complete response; MAIC, matching-adjusted indirect comparisons; nadofaragene, nadofaragene firadenovec-vncg; NAI+BCG, nogapendekin alfa inbakicept-pmln in combination with BCG.aNot feasible due to reinduction in QUILT 3.032, which affected response timing and duration, precluding a valid 12‑month comparison.
  • Safety results were not reported in the study.
MAIC in BCG-unresponsive High-risk NMIBC with Papillary Disease Only (Cohort 4)

MAIC of INLEXZO vs Pembrolizumab in BCG-unresponsive High-risk NMIBC With Papillary-Only Disease2 
Endpoint
Overall DFS
DFS at 12 months
Adjusted HR (95% CI)
0.36 (0.20-0.64)
-
Adjusted rate difference (95% CI)
-
29 (11.6-46.2)
Abbreviations: BCG, Bacillus Calmette-Guérin; CI, confidence interval; DFS, disease-free survival; HR, hazard ratio; MAIC, matching-adjusted indirect comparisons; NMIBC, nonmuscle-invasive bladder cancer.
  • Comparisons with nadofaragene and NAI + BCG were not feasible due to the limited sample size of the CS003 papillary cohort (n=48) and nonreconstructable survival data, respectively.

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 02 June 2026.

 

References

Show
1 Daneshmand S, van der Heijden MS, Jacob JM, et al. TAR-200 for Bacillus Calmette-Guérin–unresponsive high-risk non–muscle-invasive bladder cancer: results from the phase IIb SunRISe-1 study. J Clin Oncol. 2025;43(33):3578-3588.  
2 Daneshmand S, Côté S, Jain R, et al. Matching-adjusted indirect comparisons of gemcitabine intravesical system vs novel agents in Bacillus Calmette-Guérin-unresponsive high-risk non-muscle invasive bladder cancer. JU Open Plus. 2026;4:e00046.  
3 Douglass L, Schoenberg M. The future of intravesical drug delivery for non-muscle invasive bladder cancer. Bladder Cancer. 2016;2(3):285-292.  
4 Daneshmand S, Pohar KS, Steinberg GD, et al. Effect of GemRIS (gemcitabine-releasing intravesical system, TAR-200) on antitumor activity in muscle-invasive bladder cancer (MIBC) [abstract]. J Clin Oncol. 2017;35(Suppl. 15). Abstract e16000.  
5 Daneshmand S, Kamat AM, Shore ND, et al. Development of TAR-200: a novel targeted releasing system designed to provide sustained delivery of gemcitabine for patients with bladder cancer. Urol Oncol. 2025;43(5):286-296.  
6 Tan WS, Kelly JD. Intravesical device-assisted therapies for non-muscle-invasive bladder cancer. Nat Rev Urol. 2018;15(11):667-685.  
7 Daneshmand S, van der Heijden MS, Jacob JM, et al. Clinical protocol for: TAR-200 for Bacillus Calmette-Guérin-unresponsive high-risk non-muscle-invasive bladder cancer: results from the phase IIb SunRISe-1 study. J Clin Oncol. 2025;43(33):3578-3588.  
8 Janssen Research & Development, LLC. Phase 2b clinical study evaluating efficacy and safety of TAR-200 in combination with cetrelimab, TAR-200 alone, or cetrelimab alone in participants with high-risk non-muscle invasive bladder cancer (NMIBC) unresponsive to intravesical Bacillus Calmette-Guerin (BCG) who are ineligible for or elected not to undergo radical cystectomy. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2026 June 02]. Available from: https://clinicaltrials.gov/ct2/show/NCT04640623 NLM Identifier: NCT04640623.  
9 Daneshmand S, Brummelhuis ISG, Pohar KS, et al. The safety, tolerability, and efficacy of a neoadjuvant gemcitabine intravesical drug delivery system (TAR-200) in muscle-invasive bladder cancer patients: a phase I trial. Urol Oncol. 2022;40(7):344.e1-344.e9.  
10 Grimberg DC, Shah A, Inman BA. Overview of Taris GemRIS, a novel drug delivery system for bladder cancer. Eur Urol Focus. 2020;6(4):620-622.  
11 Daneshmand S, Côté S, Jain R, et al. Supplement to: Matching-adjusted indirect comparisons of gemcitabine intravesical system vs novel agents in Bacillus Calmette-Guérin-unresponsive high-risk non-muscle invasive bladder cancer. JU Open Plus. 2026;4:e00046.  

Would you like to clear and leave your conversation? Message history will be lost.