INLEXZO - SunRISe-2 Study

SUMMARY

• SunRISe-2 (NCT04658862) is a prospective, multicenter, open-label, randomized, phase 3 study designed to evaluate the efficacy and safety of INLEXZO plus systemic cetrelimab, an investigational immunoglobulin G4 antibody that targets the programmed cell death protein-1 (PD-1) receptor, vs concurrent chemoradiotherapy in patients with muscle-invasive bladder cancer (MIBC) who refuse or are ineligible for radical cystectomy (RC).^1-4 The primary endpoint was bladder-intact event-free survival (BI-EFS).
• Following an Independent Data Monitoring Committee (IDMC) recommendation and pre-specified interim analysis, SunRISe-2 was discontinued because the pre-defined futility criteria were met.^1,5
• Necchi et al (2026)¹ presented the efficacy and safety of the SunRISe-2 study at the data cutoff of July 7, 2025.
  • INLEXZO plus cetrelimab did not improve BI‑EFS compared with chemoradiotherapy (CRT).
  • The overall response rate (ORR) at week 18 was lower with INLEXZO plus cetrelimab (56.7%; 95% CI, 49.8-63.5) compared with CRT (65.3%; 95% CI, 58.4-71.9).
  • Treatment-related adverse events (TRAEs) leading to discontinuation were reported in 15.0% of patients receiving INLEXZO plus cetrelimab and in 9.5% of those receiving CRT.
  • No treatment-related deaths were reported with INLEXZO plus cetrelimab.

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.

BACKGROUND

• INLEXZO (gemcitabine intravesical system) is an intravesical drug releasing system (iDRS), referred to as gem-iDRS and TAR-200 in literature. INLEXZO is designed to provide local release of gemcitabine in the bladder. INLEXZO contains gemcitabine and urea minitablets within a dual-lumen silicone tube for gradual release of gemcitabine by an osmotic delivery mechanism throughout the prescribed indwelling period.^2,6-10
• INLEXZO is inserted intravesically via urinary placement catheter, after which it self-coils into a bi-oval shape (see Figure: INLEXZO iDRS). Removal of INLEXZO can be achieved using grasping forceps and cystoscopy.^10,11
• Preliminary safety and efficacy results from a phase 1b study in patients with MIBC who had INLEXZO placed prior to scheduled RC have been published.⁷

CLINICAL DATA

SunRISe-2 Study

Necchi et al (2026)¹ presented the final efficacy and safety results in patients receiving INLEXZO in combination with cetrelimab vs CRT in MIBC in the SunRISe-2 study.

Study Design/Methods

• Phase 3, prospective, multicenter, open-label, randomized study designed to evaluate the efficacy and safety of INLEXZO plus systemic cetrelimab, an investigational immunoglobulin G4 antibody that targets PD-1 receptor, vs concurrent CRT in patients with MIBC who refuse or are ineligible for RC.^2-4
• Study enrollment does not require determination of PD-1 expression.²
• The study design is shown in Figure: SunRISe-2 Study Design.

Futility Analysis

• At the data cutoff of June 28, 2024, a futility analysis based on ORR was conducted after 300 patients completed the week 18 disease assessment.
• On September 9, 2024, IDMC recommended termination of the study for futility.
• Per futility criteria, ORR with INLEXZO plus cetrelimab needed to be either higher than CRT or lower than CRT by no more than 15%. If the ORR with INLEXZO plus cetrelimab was lower than CRT by more than 15%, the IDMC would review the risks and benefits of INLEXZO plus cetrelimab to inform the nonbinding recommendation for futility.
• Enrollment was discontinued on September 11, 2024, as the prespecified futility criteria was met. At this timepoint, 518 patients were randomized (arm 1, n=262; arm 2, n=256).
  • Patients in arm 1 achieving a week 18 complete response (CR) were allowed to continue study treatment (transitioning to long-term extension), while patients in arm 2 were allowed to complete study treatment and then discontinue after the 100day safety followup.
• The final analysis includes exploratory efficacy analyses (BI-EFS, ORR, metastasis-free survival [MFS], overall survival [OS]) and safety at the clinical data cutoff date of July 7, 2025.

Results

Baseline Characteristics

• The demographics and baseline characteristics are summarized in Table: Patient Characteristics in the INLEXZO + CET and CRT Groups.

Efficacy

• At the data cutoff of July 7, 2025, the median follow-up was 11.3 (range, 0.03-43.2) months.
• The addition of cetrelimab to INLEXZO did not improve BI-EFS compared with CRT as shown in Table: BI-EFS Rates at 6 and 12 Months.

• The ORR at week 18 was lower with INLEXZO plus cetrelimab compared with CRT as summarized in Table: ORR at Week 18.

• Among patients who achieved a CR at week 18, BI-EFS rates were comparable between the two groups. The BI‑EFS rates at various timepoints are summarized in Table: BI‑EFS Rates at 6 and 12 Months Among Patients with CR at Week 18.

• MFS and OS between the two groups are shown in Table: MFS and OS in the INLEXZO + CET and CRT Groups.

Safety

• At the data cutoff of July 7, 2025, the median duration of exposure was 18.2 (range, 1-151) weeks for INLEXZO, 22.7 (range, 0-82) weeks for cetrelimab, and 6.4 (range, 0-15) weeks for CRT.
• The most frequent any-grade and grade ≥3 TRAEs in both treatment arms are summarized in Table: Summary of TRAEs.

• TRAEs leading to discontinuation were reported in 15.0% of patients treated with INLEXZO plus cetrelimab and in 9.5% of those receiving CRT.
  • Dysuria and adrenal insufficiency were the most common discontinuation‑related TRAEs with INLEXZO plus cetrelimab (1.2% each), while thrombocytopenia (1.7%) was most common with CRT.
• No treatmentrelated deaths were reported with INLEXZO plus cetrelimab, whereas one treatmentrelated death was observed in the CRT arm.

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 24 February 2026.