TAR-200 + Cetrelimab vs BCG for Bladder Cancer

(SunRISe-3 Trial)

Not currently recruiting at 433 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Muscle invasive cancer, Urethral tumors, 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: 3

Duration: Up to 5 years 2 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for individuals with high-risk bladder cancer that hasn't invaded the muscle. It evaluates whether the combination of TAR-200 (a gemcitabine-releasing system) and cetrelimab (an experimental treatment), or TAR-200 alone, can more effectively prevent cancer recurrence compared to the standard BCG treatment. Ideal candidates for this trial have never received BCG treatment and have a specific type of bladder cancer confirmed by a doctor. As a Phase 3 trial, this study represents the final step before FDA approval, providing patients an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial team for guidance.

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

Research has shown that TAR-200 is generally safe for people with bladder cancer. In earlier studies, patients tolerated TAR-200 well, and many showed no signs of cancer after treatment. Most side effects were mild.

When combined with cetrelimab, a drug that helps the immune system fight cancer, TAR-200 remains safe. Although the combination caused more side effects than cetrelimab alone, most were manageable.

In summary, both TAR-200 alone and with cetrelimab have demonstrated safety in previous studies. Most participants handled the treatments well, with side effects that were generally mild and manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for bladder cancer because they introduce novel approaches compared to standard care options like BCG therapy. Unlike standard treatments, TAR-200 is a drug-delivery system that continuously releases medication directly into the bladder over weeks, potentially enhancing efficacy and reducing side effects. Cetrelimab, on the other hand, is an immune checkpoint inhibitor that may help the immune system better target cancer cells, offering a different mechanism than BCG. Together, these approaches could provide more effective and targeted therapy options for bladder cancer patients.

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

Research has shown that TAR-200, a device that slowly releases chemotherapy directly into the bladder, yields promising results. In one study, tumors disappeared in 80% of patients, and 51% remained cancer-free after 12 months. In this trial, some participants will receive TAR-200 alone.

When combined with cetrelimab, a drug that boosts the immune system, TAR-200 also shows positive results. A study found that 38% of patients had no detectable cancer before surgery. Another group in this trial will receive the combination of TAR-200 and cetrelimab.

These findings suggest that TAR-200, both alone and with cetrelimab, could effectively treat high-risk non-muscle invasive bladder cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for individuals with high-risk non-muscle invasive bladder cancer who haven't had BCG therapy before. They should be in good enough health to participate, have no muscle-invasive or metastatic cancer, and not have significant urinary tract abnormalities that could interfere with treatment.

Inclusion Criteria

All visible signs of my bladder cancer have been surgically removed.

All side effects from my previous treatments have mostly gone away.

I have never had BCG therapy or stopped it over 3 years ago.

Exclusion Criteria

I have a history of urinating more than usual, with over 4 liters in a day.

My bladder cancer is advanced and cannot be surgically removed.

I do not have a permanent catheter, but I may use one temporarily.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either TAR-200 in combination with cetrelimab, TAR-200 alone, or intravesical BCG

Up to 5 years 2 months

Weekly visits for BCG group, every 3 weeks for TAR-200 groups

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years 2 months

What Are the Treatments Tested in This Trial?

Interventions

• BCG Vesiculture
• Cetrelimab
• TAR-200

Trial Overview The study compares the effectiveness of TAR-200 combined with cetrelimab (Group A) and TAR-200 alone (Group C) against intravesical BCG therapy (Group B). The main goal is to see which group stays free from cancer events longer.

How Is the Trial Designed?

Group I: Treatment Group C: TAR-200 Alone Experimental Treatment 1 Intervention

Participants will receive intravesical TAR-200 alone once Q3W.

Group II: Treatment Group A: TAR-200 + Cetrelimab Experimental Treatment 2 Interventions

Participants will receive intravesical TAR-200 once every 3 weeks (Q3W) and cetrelimab.

Group III: Treatment Group B: Bacillus Calmette-Guerin (BCG) Vesiculture Active Control 1 Intervention

Participants will receive intravesical BCG once every week for 6 weeks (induction) and then followed by once every week for 3 weeks starting at Weeks 12, 24, 48, 72, and 96 (maintenance).

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

In a study of 35 patients with BCG-refractory superficial bladder cancer, intravesical Gemcitabine demonstrated a 60% success rate in preventing tumor recurrences over an 18-month follow-up period.

The treatment was well tolerated with low and mild adverse events, making Gemcitabine a promising alternative for patients who do not respond to BCG therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of BCG non-responders with fixed dose intravesical gemcitabine in superficial transitional cell carcinoma of urinary bladder. Mohanty, NK., Nayak, RL., Vasudeva, P., et al.[2021]

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 study of 80 patients with high-risk non-muscle-invasive bladder cancer who failed BCG therapy, intravesical gemcitabine significantly reduced the disease recurrence rate (52.5%) compared to BCG (87.5%), indicating its potential as an effective second-line treatment option.

Kaplan-Meier analysis showed that gemcitabine provided a higher 2-year recurrence-free survival rate (19%) compared to BCG (3%), suggesting that gemcitabine may offer better long-term outcomes for patients after BCG failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine versus bacille Calmette-Guérin after initial bacille Calmette-Guérin failure in non-muscle-invasive bladder cancer: a multicenter prospective randomized trial. Di Lorenzo, G., Perdonà, S., Damiano, R., et al.[2022]

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]

In a study of 35 patients with BCG failure, intravesical gemcitabine demonstrated a 60% success rate in preventing tumor recurrences over an 18-month follow-up period, indicating its efficacy as an alternative treatment.

The treatment was well tolerated with low and mild adverse events, suggesting that gemcitabine is a safe option for patients who do not respond to BCG therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesicle gemcitabine in management of BCG refractory superficial TCC of urinary bladder-our experience. Mohanty, NK., Nayak, RL., Vasudeva, P., et al.[2022]

Intravesical gemcitabine (Gem) shows a lower incidence of side effects like dysuria and hematuria compared to Bacille Calmette-Guérin (BCG) in treating non-muscle invasive bladder cancer, based on a meta-analysis of 386 subjects from 5 trials.

Both treatments have similar efficacy in terms of recurrence and progression rates, indicating that Gem could be a safer alternative to BCG, but further high-quality trials are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of intravesical gemcitabine vs Bacille Calmette-Guérin for adjuvant treatment of non-muscle invasive bladder cancer: a meta-analysis. Ye, Z., Chen, J., Hong, Y., et al.[2022]

Intravesical gemcitabine and docetaxel therapy shows promising efficacy for high-risk nonmuscle invasive bladder cancer, with 1-year and 2-year recurrence-free survival rates of 86% and 84% in BCG-naive patients, and 80%, 66%, and 51% in BCG-unresponsive patients at 6 months, 1 year, and 2 years, respectively.

The treatment is generally well tolerated, with only 2.3% of patients unable to complete induction therapy and 6.9% experiencing delays or dose reductions due to adverse events, suggesting it could be a viable alternative to BCG therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential intravesical gemcitabine and docetaxel therapy in patients with nonmuscle invasive bladder cancer: a systematic review and meta-analysis. Kawada, T., Yanagisawa, T., Araki, M., et al.[2023]

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. 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– ...

3. oncology-central.com oncology-central.com/slow-release-gemcitabine-device-targets-bladder-cancer-more-effectively/

Slow–release gemcitabine device targets bladder cancer ... A slow–release device termed TAR-200, which releases a common chemotherapy agent over 3 weeks eliminated tumors in 80% of patients studied.

4. 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 TAR-200 is a novel targeted releasing system designed to provide sustained intravesical delivery of gemcitabine within the bladder. 18 ...

5. trialx.com trialx.com/tar-200-bladder-cancer-treatment/

TAR-200's Potential in Bladder Cancer Treatment Among 83 evaluable patients, the complete response (CR) rate was 82% (95% CI: 72–90). At 12 months, 51% of responders remained in CR. Safety ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10998271/

A Phase 1b Study - PubMed Central - NIH In this phase 1b study, TAR-200, a novel drug delivery system, was safe and well tolerated in participants with intermediate-risk non–muscle-invasive bladder ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02722538

NCT02722538 | Safety and Tolerability of GemRIS 225 mg ... The purpose of this study is to determine if TAR-200, an investigational drug-delivery system, is safe and tolerable in patients with muscle-invasive bladder ...

8. innovativemedicine.jnj.com innovativemedicine.jnj.com/emea/newsroom/johnson-johnsons-tar-200-monotherapy-demonstrates-highest-complete-response-rate-reported-to-date-with-sustained-clinical-benefits-in-patients-with-certain-types-of-bladder-cancer

Johnson & Johnson's TAR-200 monotherapy demonstrates ... TAR-200 monotherapy shows greater than 80 percent complete response rate in patients with high-risk non-muscle-invasive bladder cancer.