INLEXZO - Comparison to Nogapendekin alfa inbakicept-pmin

SUMMARY

• INLEXZO (gemcitabine intravesical system) is an intravesical drug releasing system (iDRS), referred to as gem-iDRS and TAR-200 in literature.​¹ 
• No prospective, randomized, head-to-head trials comparing the efficacy and safety of INLEXZO with nogapendekin alfa inbakicept have been conducted.
• Daneshmand et al (2026)² conducted a matching-adjusted indirect comparison (MAIC) study to compare the relative treatment of INLEXZO vs United States (US) Food and Drug Administration (FDA)-approved novel agents (pembrolizumab, nadofaragene firadenovec-vncg [nadofaragene], and nogapendekin alfa inbakicept-pmln in combination with Bacillus Calmette-Guérin [NAI + BCG]) in 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 and at first disease assessment were assessed against NAI + BCG.
  • The adjusted CR rate at any time for INLEXZO vs NAI + BCG was 83% vs 62% (absolute rate difference, 21% [95% confidence interval (CI), 7%-35%]; P=0.003).
  • The CR rate at the first disease assessment for INLEXZO vs NAI + BCG was 82% vs 45% (absolute rate difference, 36% [95% CI, 22%-51%]; P<0.001), based on calculated data that excluded patients who received a second induction of NAI + BCG.
  • 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.
• Jayram et al (2026)³ conducted a MAIC to compare 12‑month CR rate and treatment‑related adverse events (TRAEs) of NAI + BCG vs INLEXZO in patients with BCG‑unresponsive NMIBC. Patient‑level data from QUILT‑3.032 (NAI + BCG) were weighted to match aggregate data of baseline characteristics (age ≥65 years, sex, Eastern Cooperative Oncology Group [ECOG] performance status, prior BCG, and tumor stage) of SunRISe‑1 (Cohort 2), with effective sample size assessed to ensure adequate matching.
  • CR rates at 12 months were 49.6% with NAI + BCG vs 45.9% with INLEXZO; odds ratio [OR], 1.16 [95% CI, 0.60-2.24]).
  • Any grade TRAE rates were 61.7% with NAI + BCG vs 83.5% with INLEXZO; adjusted analysis showed significantly lower odds of TRAEs with NAI + BCG (OR, 0.32 [95% CI, 0.15­0.67]).
  • Results were consistent across adjusted, unadjusted, and sensitivity analyses, supporting robustness of findings, although interpretation should consider limitations inherent to unanchored MAIC methodology.

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.

MAIC 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 NAI + BCG in patients with 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 NAI+BCG (QUILT 3.032).
• 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 US prescribing information (USPI) and primary publications of QUILT 2.032.
• Study and patient characteristics, patient eligibility criteria, outcome definitions, and reporting timing for SunRISe-1 and NAI + BCG (QUILT 3.032) were evaluated to assess the feasibility of conducting a MAIC.
• Unanchored MAICs for the CIS cohort and papillary-only cohort were conducted using individual patient data (IPD) from SunRISe-1 Cohorts 2 and 4, respectively.
• Adjustment of imbalances in patient characteristics (tumor stage, prior doses of BCG instillation, Eastern Cooperative Oncology Group, age, gender, and race) was performed by weighting the INLEXZO IPD to match baseline characteristics reported for QUILT 3.032.
• 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 NAI + BCG.
  • 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 not feasible between INLEXZO 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.
  • 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.

Trial Characteristics

• Treatment characteristics and CR definitions across the SunRISe-1 and QUILT 3.032 trials are summarized in Table: Comparison of Treatment Characteristics and CR Definitions Among Trials Investigating INLEXZO or NAI + BCG for BCG-Unresponsive High-Risk NMIBC With CIS.

Patient Characteristics

• Baseline patient characteristics across the SunRISe-1 and QUILT 3.032 trials after matching are included in Table: Baseline Patients Characteristics Across the SunRISe-1 and QUILT 3.032 Trials.

MAIC in BCG-unresponsive High-risk NMIBC With CIS ± Papillary Disease (Cohort 2)

• The adjusted CR rate at any time for INLEXZO vs NAI + BCG was 83% vs 62% (absolute rate difference, 21% [95% CI, 7%-35%]; P=0.003).
• The absolute rate difference of CR at the first disease assessment of INLEXZO vs NAI + BCG was 82% vs 45% (adjusted, 36% [95% CI; 22%-51%], P<0.001; unadjusted, 34% [95% CI, 20%-48%]).
• A comparison of 12month CR rates between INLEXZO and NAI + BCG was not feasible, due to differences in response timing and duration resulting from reinduction in QUILT 3.032.
• Safety results were not reported in the study.

MAIC in BCG-unresponsive High-risk NMIBC with Papillary Disease Only (Cohort 4)

• Comparisons of INLEXZO and NAI + BCG were not feasible in QUILT 3.032 due to absence of numberatrisk data in the Kaplan–Meier analysis.

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) conducted on 03 June 2026.