TAR-200 + Cetrelimab vs Chemoradiotherapy for Bladder Cancer

(SunRISe-2 Trial)

Not currently recruiting at 469 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Urothelial carcinoma, Diffuse CIS, cT4b/N1-3/M1 disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 18 weeks initial, then every 12 weeks through Year 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for bladder cancer. It compares TAR-200 (a gemcitabine-releasing system) plus cetrelimab (an experimental treatment) to the usual chemoradiotherapy (a mix of chemotherapy and radiation). The goal is to determine which option helps patients maintain bladder health for longer. Individuals who cannot or choose not to undergo bladder removal surgery, and have a stable health condition, might be suitable candidates for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of TAR-200 and cetrelimab is promising and generally well-tolerated by patients. An early analysis from a study found that many patients experienced significant tumor shrinkage, with most side effects being manageable.

However, treatment-related side effects did occur. One report indicated that 72% of patients experienced some side effects, mostly mild. More serious side effects were less common. This suggests that while risks exist, many patients can handle the treatment without major problems.

Overall, these findings suggest that the combination of TAR-200 and cetrelimab is relatively safe for many patients, but discussing potential risks with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about TAR-200 and Cetrelimab for bladder cancer because they offer a fresh approach compared to the standard treatment of chemotherapy and radiation. Unlike traditional methods, TAR-200 delivers medication directly to the bladder, providing targeted therapy that may minimize side effects. Cetrelimab, on the other hand, is an immunotherapy drug that boosts the body's immune system to fight cancer cells more effectively. This combination could potentially improve outcomes and reduce the treatment burden for patients with bladder cancer.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

In this trial, participants will receive either the combination of TAR-200 and cetrelimab or chemotherapy with radiation therapy. Research has shown promising results for the combination of TAR-200 and cetrelimab in treating bladder cancer. One study demonstrated a high rate of complete response, meaning the cancer could not be found after treatment. Another study found this treatment effective before surgery, with 38% of patients having no detectable cancer in their bladder. TAR-200, when used with cetrelimab, was also found to be safe, with manageable side effects. These findings suggest that this treatment could be a strong option for those with muscle-invasive bladder cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trials

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for adults with muscle-invasive bladder cancer who can't have or chose not to get radical cystectomy. They should be relatively active (ECOG 0-2), recovered from previous treatments, and have normal thyroid function plus good bone marrow, liver, and kidney health.

Inclusion Criteria

Your thyroid test results are normal, or if you're taking medication for your thyroid, it's stable. If your test results are not clear, a specialist may be consulted to decide if you can participate.

I can take care of myself but might not be able to do heavy physical work.

I have chosen not to or cannot have major bladder surgery.

Exclusion Criteria

My bladder was accidentally punctured during a bladder exam but has since healed.

My bladder cancer has not spread outside the bladder, except for specific treated cases over 2 years ago.

You have a bladder or urethral feature that could make it difficult or unsafe to use the TAR 200 device.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TAR-200 every 3 weeks for the first 18 weeks and thereafter from Week 24 every 12 weeks through study Year 3 in combination with intravenous Cetrelimab or chemotherapy with radiation therapy

18 weeks initial, then every 12 weeks through Year 3

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 8 years

What Are the Treatments Tested in This Trial?

Interventions

• Cetrelimab
• Cisplatin
• Conventional radiation therapy
• Gemcitabine
• Hypo-fractioned radiation therapy
• TAR-200

Trial Overview The study compares the effectiveness of TAR-200 combined with cetrelimab against standard chemoradiotherapy in preserving the bladder. Participants are randomly assigned to either treatment group to measure which approach is better at preventing cancer progression.

How Is the Trial Designed?

Group I: TAR-200 + Cetrelimab Experimental Treatment 2 Interventions

Participants will receive intravesical TAR-200 every 3 weeks (21 days indwelling) for first 18 weeks and thereafter from Week 24 every 12 weeks through study Year 3 in combination with intravenous (IV) Cetrelimab.

Group II: Chemotherapy (cisplatin or gemcitabine) + Radiation Therapy Active Control 4 Interventions

Participants will receive chemotherapy based on investigator's choice from either cisplatin intravenously once weekly for 4 to 6 treatment weeks or gemcitabine intravenously twice weekly for 4 to 6 treatment weeks as Standard of Care (SOC) along with radiation therapy from either conventional radiotherapy (64 Gray \[Gy\], bladder only) for up to 6.5 treatment weeks or hypo-fractionated radiotherapy (55 Gy, bladder only) for up to 4 weeks.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

Pembrolizumab significantly improves survival and quality of life for patients with advanced urothelial cancer who cannot tolerate cisplatin-based chemotherapy, offering an increase of approximately 2.11 to 2.16 years in overall survival and 1.71 to 1.75 quality-adjusted life years (QALYs) compared to standard treatments like carboplatin plus gemcitabine and gemcitabine monotherapy.

Despite being associated with higher costs (an increase of €90,520 compared to carboplatin plus gemcitabine), pembrolizumab is considered cost-effective at a threshold of €100,000/QALY, making it a viable first-line treatment option for this patient population in Sweden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy. Patterson, K., Prabhu, V., Xu, R., et al.[2022]

TAR-200, a novel drug delivery system for gemcitabine, was found to be generally safe and well tolerated in a study of 35 elderly patients with muscle-invasive bladder cancer who were unfit for standard treatment.

The treatment showed promising preliminary efficacy, with a 40% overall response rate and a median overall survival of 27.3 months, indicating it could be a valuable option for patients with limited treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Preliminary Efficacy of TAR-200 in Patients With Muscle-invasive Bladder Cancer Who Refused or Were Unfit for Curative-intent Therapy: A Phase 1 Study. Tyson, MD., Morris, D., Palou, J., et al.[2023]

In a phase 2 study involving 45 patients with invasive bladder cancer, the combination of radiation therapy and atezolizumab resulted in a high pathologic complete response (pCR) rate of 84.4%, particularly in older patients and those with high PD-L1 expression.

The treatment was associated with acceptable toxicity, with 93.3% of patients experiencing adverse events, mostly mild to moderate, and only 13.3% experiencing grade 3 adverse events, indicating that this approach could be a viable bladder-preserving option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial. Kimura, T., Ishikawa, H., Nagumo, Y., et al.[2023]

The TAR-200 system for delivering gemcitabine directly into the bladder was found to be safe and well tolerated in a phase I study involving 23 patients with muscle-invasive bladder cancer (MIBC), with no intolerable side effects reported.

Preliminary efficacy results showed that a significant number of patients experienced pathologic downstaging after treatment, with some achieving complete or partial responses, indicating potential effectiveness of this localized treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Daneshmand, S., Brummelhuis, ISG., Pohar, KS., et al.[2022]

Neoadjuvant chemotherapy has been shown to improve overall survival in patients with locally advanced muscle-invasive bladder cancer, but its use in clinical practice remains low due to ongoing controversies regarding adjuvant chemotherapy.

Recent advancements include the approval of atezolizumab, a checkpoint inhibitor, for metastatic bladder cancer, alongside other promising therapies targeting mutational signatures, such as VEGF and HER2-directed agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises. Aragon-Ching, JB., Trump, DL.[2017]

Atezolizumab has been approved by the FDA as a treatment for advanced bladder cancer, specifically for patients who cannot receive cisplatin chemotherapy.

This approval provides a potentially more effective treatment option compared to carboplatin-based chemotherapy, particularly for frail and elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nod for Atezolizumab in Advanced Bladder Cancer. [2018]

Atezolizumab, an anti-PD-L1 monoclonal antibody, has shown durable responses in treating locally advanced and metastatic urothelial cancer, especially in patients who have failed platinum-based chemotherapy or are ineligible for cisplatin.

The treatment with atezolizumab has a more favorable toxicity profile compared to traditional cytotoxic chemotherapy, making it a promising option for patients with advanced bladder cancer, although further research is needed to identify additional predictive markers for response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in invasive and metastatic urothelial carcinoma. Crist, M., Balar, A.[2019]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-01651

TAR-200 for Bacillus Calmette-Guérin–Unresponsive High- ... In phase I studies, TAR-200 was well tolerated and showed preliminary efficacy in patients with muscle-invasive bladder cancer and intermediate ...

2. jnj.com jnj.com/media-center/press-releases/johnson-johnsons-inlexzo-gemcitabine-intravesical-system-plus-cetrelimab-delivers-strong-pre-surgical-results-in-patients-with-muscle-invasive-bladder-cancer-scheduled-for-radical-cystectomy

Johnson & Johnson's INLEXZO™ (gemcitabine intravesical ... Phase 2b SunRISe-4 study shows 38% of patients treated with INLEXZO™-based combination had no detectable cancer in the bladder prior to surgery

3. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00358-4/fulltext?rss=yes

interim analysis of a randomised, open-label phase 2 trial Neoadjuvant TAR-200 plus cetrelimab showed a high pathological complete response rate with a manageable safety profile. These results support ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1078143924010445

Development of TAR-200: A novel targeted releasing ... Preliminary data from the phase IIb SunRISe-1 study demonstrate that TAR-200 monotherapy is safe and effective in patients with bacillus Calmette-Guérin– ...

5. ascopost.com ascopost.com/news/september-2025/addition-of-neoadjuvant-tar-200-to-cetrelimab-in-cisplatin-ineligible-muscle-invasive-bladder-cancer/

Addition of Neoadjuvant TAR-200 to Cetrelimab in ... Treatment-related adverse events of any grade occurred in 72% of the TAR-200/cetrelimab group vs 44% of the cetrelimab group; grade ≥ 3 events ...