TAR-200 + Cetrelimab for Bladder Cancer

(SunRISe-4 Trial)

Recruiting at 137 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

Must not be taking: Chemotherapy, Radiation therapy

Disqualifiers: Small cell, Neuroendocrine, cT4b, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 15 weeks

163 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the anti-tumor effects of TAR-200 in combination with intravenous (IV) cetrelimab and IV cetrelimab alone.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have had chemotherapy, targeted therapy, or radiation therapy within 2 weeks before starting the study treatment.

What data supports the effectiveness of the treatment TAR-200 + Cetrelimab for bladder cancer?

Research shows that TAR-200, which releases gemcitabine directly into the bladder, has been found to be safe and shows preliminary effectiveness in patients with muscle-invasive bladder cancer who cannot undergo standard treatments. Additionally, gemcitabine has shown promising activity in improving survival in patients with metastatic bladder cancer. ^{1 2 3 4 5}

Is the TAR-200 treatment safe for bladder cancer patients?

TAR-200, a system that releases gemcitabine directly into the bladder, has been studied for safety in patients with muscle-invasive bladder cancer. The studies found it to be generally safe and tolerable for patients who were either unfit for or refused more aggressive treatments. ^{2 3 4 6 7}

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

TAR-200 is a unique treatment for bladder cancer because it uses an intravesical drug delivery system to release gemcitabine directly into the bladder over a 21-day cycle, providing localized treatment with potentially fewer systemic side effects. Cetrelimab, combined with TAR-200, may enhance the immune response against cancer cells, offering a novel approach compared to traditional systemic therapies. ^{2 3 5 7 8}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults with muscle-invasive bladder cancer that hasn't spread beyond the bladder and who haven't had systemic chemotherapy or radiation recently. They should be in good physical condition (ECOG 0-1) and have normal thyroid function or stable hormone levels. Tumors must be predominantly urothelial, not larger than 3cm after surgery, and participants must be fit for radical cystectomy.

Inclusion Criteria

My urologist says I can and should have radical cystectomy.

Your thyroid tests are normal, or if you are taking thyroid medication, it's working well for you. If the test results are unclear, a specialist may be consulted to decide if you can participate.

My bladder cancer was diagnosed within the last 4 months and is not spread to other parts.

Exclusion Criteria

I have had chemotherapy for bladder cancer before.

I haven't had chemotherapy, targeted therapy, or radiation in the last 2 weeks.

I haven't been in a clinical trial for a new treatment or device in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TAR-200 in combination with cetrelimab or cetrelimab alone

15 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

108 weeks

Treatment Details

Interventions

• Cetrelimab
• TAR-200

Trial Overview The study tests TAR-200 inserted into the bladder combined with cetrelimab given through IV, versus cetrelimab alone via IV. The goal is to see which treatment better reduces tumor size or prevents cancer from returning.

Participant Groups

Group I: Cohort 2: Cetrelimab Experimental Treatment 1 Intervention

Participants will receive cetrelimab.

Group II: Cohort 1: TAR-200 + Cetrelimab Experimental Treatment 2 Interventions

Participants will receive TAR-200 in combination with cetrelimab.

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

Gemcitabine maintenance therapy after standard platinum-gemcitabine treatment in metastatic bladder cancer patients showed a median progression-free survival (PFS) of 46 weeks, indicating a potential benefit in extending survival for those who responded to initial treatment.

The treatment was associated with a low toxicity profile, with only 30.4% of patients experiencing grade 3 hematotoxicity, suggesting that gemcitabine maintenance is a relatively safe option for improving outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance treatment with gemcitabine have a promising activity on metastatic bladder cancer survival. Kuş, T., Aktaş, G.[2020]

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]

The combination of gemcitabine and irinotecan (Irinogem) showed promising efficacy in treating metastatic bladder cancer, with 8 out of 13 evaluable patients achieving an objective response, including 2 complete responses and 6 partial responses, and a median progression-free survival of 8.78 months.

The treatment was associated with manageable toxicity, with no toxic deaths reported, although some patients experienced significant side effects like neutropenia and diarrhea. However, the study's early closure due to funding issues limits the ability to draw definitive conclusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of gemcitabine and irinotecan in patients with locally advanced or metastatic bladder cancer. Chaudhary, UB., Verma, N., Keane, T., 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]

In a Phase II study involving 56 elderly and unfit patients with advanced bladder carcinoma, the combination of gemcitabine and carboplatin showed a 36% overall response rate, indicating its efficacy as a first-line treatment.

The treatment was associated with manageable toxicity, with significant side effects including neutropenia (27%) and anemia (18%), but it still represents a viable option for patients who cannot tolerate cisplatin-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and carboplatin combination as first-line treatment in elderly patients and those unfit for cisplatin-based chemotherapy with advanced bladder carcinoma: Phase II study of the Hellenic Co-operative Oncology Group. Linardou, H., Aravantinos, G., Efstathiou, E., et al.[2022]

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]

Urothelial carcinoma, the most common urological cancer, is primarily treated with Bacillus Calmette-Guerin (BCG) immunotherapy for superficial cases and cisplatin-based chemotherapy for metastatic disease, with vinflunine as the standard second-line option in Europe.

Novel PD-1/PD-L1 inhibitors like atezolizumab, nivolumab, and pembrolizumab have shown promise in treating bladder cancer, particularly for patients who cannot tolerate cisplatin, and are generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. Büchler, T.[2019]

References

1. Turkey pubmed.ncbi.nlm.nih.gov

Maintenance treatment with gemcitabine have a promising activity on metastatic bladder cancer survival. [2020]

2. 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]

3. 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]

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

A phase II study of gemcitabine and irinotecan in patients with locally advanced or metastatic bladder cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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

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

Gemcitabine and carboplatin combination as first-line treatment in elderly patients and those unfit for cisplatin-based chemotherapy with advanced bladder carcinoma: Phase II study of the Hellenic Co-operative Oncology Group. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Atezolizumab in invasive and metastatic urothelial carcinoma. [2019]

8. Czech Republic pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. [2019]