TAR-200 + Cetrelimab vs BCG for Bladder Cancer

(SunRISe-3 Trial)

Recruiting at 376 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

1135 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new bladder cancer treatment using a special device to deliver a drug directly into the bladder, either alone or with an immune-boosting drug. It targets patients with high-risk bladder cancer who haven't had BCG treatment before. The device ensures a steady release of the drug, while the immune-boosting drug helps the body fight cancer.

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.

What data supports the effectiveness of the treatment TAR-200 + Cetrelimab vs BCG for Bladder Cancer?

Research shows that gemcitabine, a component of the TAR-200 treatment, is effective as an alternative to BCG for patients with non-muscle invasive bladder cancer, especially after BCG failure. This suggests that TAR-200, which releases gemcitabine, could be a promising option for bladder cancer treatment. ^{1 2 3 4 5}

Is TAR-200 safe for bladder cancer treatment?

TAR-200, a system that releases gemcitabine into the bladder, has been studied for safety in patients with muscle-invasive bladder cancer, showing it is generally safe for use in humans. ^{2 3 5 6 7}

How is the TAR-200 + Cetrelimab treatment different from other bladder cancer treatments?

The TAR-200 + Cetrelimab treatment is unique because it uses a novel drug delivery system (TAR-200) that continuously releases gemcitabine directly into the bladder, providing a localized treatment over a 21-day cycle, which may reduce systemic side effects compared to traditional chemotherapy. ^{1 2 3 6 8}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

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]

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 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]

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]

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-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]

References

1. United States 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Real-world efficacy of adjuvant single-agent intravesical gemcitabine for non-muscle invasive bladder cancer. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Intravesicle gemcitabine in management of BCG refractory superficial TCC of urinary bladder-our experience. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Sequential intravesical gemcitabine and docetaxel therapy in patients with nonmuscle invasive bladder cancer: a systematic review and meta-analysis. [2023]

5. New Zealand 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. [2022]

6. United States 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. [2022]

7. India pubmed.ncbi.nlm.nih.gov

Management of BCG non-responders with fixed dose intravesical gemcitabine in superficial transitional cell carcinoma of urinary bladder. [2021]

8. United States 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. [2023]