TAR-200 + Cetrelimab for Bladder Cancer

(SunRISe-1 Trial)

Not currently recruiting at 211 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

Must not be taking: Anti-PD-1 agents

Disqualifiers: Muscle-invasive cancer, Hepatitis B/C, 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: Up to 99 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, TAR-200 and cetrelimab, to evaluate their effectiveness for certain types of bladder cancer. TAR-200 is a gemcitabine-releasing system, while cetrelimab is an experimental treatment. Researchers aim to determine which combination helps more participants experience no signs of cancer and remain disease-free longer. Participants will be divided into groups: some will receive both treatments, some just one, and others a different combination. Those with high-risk bladder cancer who have not responded to a therapy called BCG might be suitable for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for 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 coordinators or your doctor.

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 patients. It delivers medicine directly into the bladder and is well-tolerated by most people. Serious side effects are rare, and it has proven effective in treating bladder cancer. In one study, over 80% of patients responded well to the treatment.

Cetrelimab, another treatment under study, also appears safe. Most reported side effects were mild to moderate, such as fatigue or slight bladder irritation, with serious side effects being less common. When used together, TAR-200 and cetrelimab have shown similar safety results, with most side effects being minor.

Overall, both TAR-200 and cetrelimab have demonstrated promising safety results in studies. However, discussing any potential risks with a healthcare provider is important. ^{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 bring innovative approaches compared to current treatments like surgery, chemotherapy, or immunotherapy, such as BCG. TAR-200 offers a novel delivery method, where medication is directly placed into the bladder via a catheter, allowing for a sustained and localized release, which could improve efficacy and reduce systemic side effects. Cetrelimab, on the other hand, is an immunotherapy that targets PD-1, potentially boosting the body's immune response against cancer cells. Together, these treatments could offer more targeted and effective options for patients, especially for those with carcinoma in situ (CIS) or papillary disease.

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

Research has shown that TAR-200, one of the treatments in this trial, holds promise for treating bladder cancer, with many patients experiencing quick and complete recovery within the first three months. Studies have found that over 80% of patients remain disease-free at nine months, especially those unresponsive to earlier treatments. Cetrelimab, another treatment option in this trial, is a drug that helps the immune system fight cancer and has successfully kept 82% of patients in complete recovery over an average follow-up of 9.2 months. When TAR-200 is combined with cetrelimab, as in one of the trial's treatment arms, evidence indicates better results, particularly for patients who did not respond to standard treatments. This combination shows a high rate of complete recovery with manageable side effects. ^{2 4 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 adults with high-risk non-muscle invasive bladder cancer that hasn't responded to BCG therapy and who can't have or chose not to undergo bladder removal surgery. They should be mostly urothelial cancer type, without certain aggressive features, and must have a performance status that allows daily living activities.

Inclusion Criteria

I am able to care for myself and perform daily activities.

My bladder cancer did not respond to a full course of BCG treatment.

My tumor is mainly urothelial but doesn’t have certain aggressive features.

Exclusion Criteria

I have not received a live virus vaccine in the last 30 days.

I don't have active hepatitis B or C, or it's undetectable.

My bladder cancer has not spread outside the bladder, except possibly for early-stage cancer in the upper urinary tract treated over 2 years ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TAR-200 and/or Cetrelimab based on cohort assignment. TAR-200 is dosed every 3 weeks for up to 24 weeks, then every 12 weeks through Week 99. Cetrelimab is dosed every 3 weeks through Week 78.

Up to 99 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of complete response rate and disease-free survival.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cetrelimab
• TAR-200

Trial Overview The study tests TAR-200 (a drug-device combination) and Cetrelimab (an immunotherapy), alone or in combination, in four different participant groups based on their specific type of bladder cancer. The main goals are to see if the treatments completely remove the cancer or prevent it from returning.

How Is the Trial Designed?

Group I: Cohort 4: TAR-200 (Participants with Papillary Disease only) Experimental Treatment 1 Intervention

TAR-200 is placed into the bladder through a urinary placement catheter in participants with papillary disease only, on Day 0 and will be dosed Q3W for up to the first 24 weeks (6 months), then every 12 weeks through Week 99 (Year 2).

Group II: Cohort 3: Cetrelimab Experimental Treatment 1 Intervention

Participants with CIS, with or without papillary disease, will receive Cetrelimab which will be dosed Q3W through Week 78 (18 months).

Group III: Cohort 2: TAR-200 Experimental Treatment 1 Intervention

TAR-200 is placed into the bladder through a urinary placement catheter in participants with CIS, with or without papillary disease, on Day 0 and will be dosed Q3W for up to the first 24 weeks (6 months), then every 12 weeks through Week 99 (Year 2).

Group IV: Cohort 1: TAR-200 and Cetrelimab Experimental Treatment 2 Interventions

TAR-200 is placed into the bladder through a urinary placement catheter in participants with carcinoma in situ (CIS), with or without papillary disease, on Day 0 and will be dosed every 3 weeks (Q3W) for up to the first 24 weeks (6 months), then every 12 weeks through Week 99 (Year 2). In addition, Cetrelimab will be dosed Q3W through Week 78 (18 months).

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

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]

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 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]

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]

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]

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]

Citations

1. jnj.com jnj.com/innovativemedicine/emea/newsroom/oncology/new-data-from-tar-200-phase-2b-sunrise-1-study-show-84-percent-complete-response-rate-in-patients-with-high-risk-non-muscle-invasive-bladder-cancer

New data from TAR-200 Phase 2b SunRISe-1 study show ... Results show highly durable CRs without the need for reinduction, with 82 percent of patients maintaining response after a median follow-up of 9.2 months and an ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-01651

TAR-200 for Bacillus Calmette-Guérin–Unresponsive High- ... TAR-200 alone or in combination with cetrelimab (PD-1 inhibitor) could improve outcomes in patients with bacillus Calmette-Guérin (BCG)– ...

3. 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 ...

4. urotoday.com urotoday.com/conference-highlights/esmo-2024/esmo-2024-bladder-cancer/154852-esmo-2024-tar-200-cetrelimab-and-cetrelimab-alone-in-patients-with-bcg-unresponsive-high-risk-nmibc-updated-results-from-sunrise-1.html

ESMO 2024: TAR-200 +/- Cetrelimab and ... Overall, most adverse events were grade 1 or 2, with higher rates of grade >= 3 treatment related adverse events were observed with the ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05714202

NCT05714202 | A Study of TAR-200 in Combination With ... The purpose of this study is to compare event-free survival (EFS) in participants with Bacillus Calmette-Guerin (BCG)-naive high-risk non-muscle invasive ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05714202

NCT05714202 | A Study of TAR-200 in Combination With ... The purpose of this study is to compare event-free survival (EFS) in participants with Bacillus Calmette-Guerin (BCG)-naive high-risk non-muscle invasive ...

7. 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

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03909-7/fulltext

LBA85 TAR-200 +/- cetrelimab (CET) and CET alone in ... At May 13, 2024 data cutoff, 53 pts in C1, 85 in C2, and 28 in C3 were treated (median age 71.5 y, 80% male, 31% papillary disease). Centrally confirmed CR ...