TAR-200 + Cetrelimab vs Chemoradiotherapy for Bladder Cancer

(SunRISe-2 Trial)

Recruiting at 379 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

518 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment for bladder cancer that combines a device delivering medication directly to the bladder with a drug that helps the immune system fight cancer. The goal is to see if this combination works better than the usual treatment in keeping the bladder free from cancer events.

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.

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

Research shows that combining cisplatin and radiation can enhance the effectiveness of immune therapies like anti-PD-1 treatments in bladder cancer, leading to better response rates and survival. This suggests that similar combinations, like TAR-200 with Cetrelimab, might also be effective. ^{1 2 3 4 5}

Is the combination of TAR-200 and Cetrelimab safe for humans?

TAR-200, which releases gemcitabine into the bladder, has been studied for safety in patients with muscle-invasive bladder cancer, showing it is generally safe and tolerable. However, specific safety data for the combination of TAR-200 and Cetrelimab is not provided in the available research. ^{6 7 8 9 10}

What makes the TAR-200 + Cetrelimab treatment unique for bladder cancer?

The TAR-200 + Cetrelimab treatment is unique because it combines a localized drug delivery system (TAR-200) that releases gemcitabine directly into the bladder with Cetrelimab, an immune checkpoint inhibitor, potentially enhancing the immune system's ability to fight cancer cells. This approach differs from traditional systemic chemotherapy by targeting the tumor more directly and may reduce systemic side effects. ^{2 3 9 10 11}

Research Team

Janssen Research & Development, LLC Clinical Trials

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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

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]

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]

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]

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]

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]

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, 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]

References

1. Egypt pubmed.ncbi.nlm.nih.gov

Three-Dimensional Conformal Radiotherapy Combined with Gemcitabine and Docetaxel in the Treatment of Advanced Bladder Cancer and Its Effects on Inflammatory Factors and Immune Function. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Biweekly carboplatin/gemcitabine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: report of efficacy, quality of life and geriatric assessment. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Combination of Cisplatin and Irradiation Induces Immunogenic Cell Death and Potentiates Postirradiation Anti-PD-1 Treatment Efficacy in Urothelial Carcinoma. [2021]

5. United States 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. [2023]

6. 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]

7. 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]

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

Nod for Atezolizumab in Advanced Bladder Cancer. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises. [2017]

10. England pubmed.ncbi.nlm.nih.gov

Atezolizumab in invasive and metastatic urothelial carcinoma. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Atezolizumab in urothelial bladder carcinoma. [2019]