TAR-200 + Cetrelimab for Bladder Cancer

(SunRISe-4 Trial)

Not currently recruiting at 166 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating bladder cancer by testing the drug cetrelimab, both alone and with TAR-200, a device that delivers treatment directly to the bladder. The goal is to determine if these treatments can effectively reduce tumors in individuals with a specific type of bladder cancer. Suitable candidates have recently been diagnosed with certain bladder cancers and have small or no tumors following initial surgery. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that using TAR-200 with cetrelimab is generally safe. In one study, 11% of patients experienced significant side effects from this combination, while only 5% had such side effects with cetrelimab alone. This suggests that some patients might tolerate cetrelimab alone better.

Other studies have also found TAR-200 to be safe and effective on its own in similar patient groups. These results are encouraging for those considering participation in trials with these treatments. While side effects can occur, healthcare professionals usually manage and closely monitor them. ^{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 innovative approaches compared to standard treatments like chemotherapy or immunotherapy alone. TAR-200 is unique as it delivers medication directly to the bladder over time, potentially increasing the treatment's effectiveness and reducing side effects. Cetrelimab, on the other hand, is an immunotherapy that targets the PD-1 pathway, helping the immune system better recognize and attack cancer cells. Together, these treatments aim to provide a more targeted and sustained response against bladder cancer, offering hope for improved outcomes.

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

Research has shown that using TAR-200 with cetrelimab, which participants in this trial may receive, may help treat bladder cancer. One study found that this combination made the cancer undetectable in 38% of patients before surgery, meaning the tumors were completely gone. Cetrelimab alone, another treatment option in this trial, also proved effective, with 28% of patients experiencing the same result. Both treatments are generally well tolerated, allowing most patients to use them without serious side effects. This suggests that TAR-200 and cetrelimab could be effective options for treating bladder cancer. ^{1 2 3 4 6}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40885199/

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

2. 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 ...

3. 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

4. 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- ...

5. targetedonc.com targetedonc.com/view/dr-necchi-on-the-sunrise-4-study-tar-200-cetrelimab-in-bladder-cancer

Dr Necchi on TAR-200 & Cetrelimab in Bladder Cancer Results showed a significant benefit for the combination therapy. Cohort 1 achieved a pCR rate of 38% compared with 28% in the monotherapy ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04919512

NCT04919512 | A Study of TAR-200 in Combination With ... 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. Detailed ...