Immunotherapy Combo vs Chemotherapy for Bladder Cancer

(CheckMate901 Trial)

Not currently recruiting at 380 trial locations

Overseen By BMS Study Connect Contact Center http://www.bmsstudyconnect.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Must not be taking: Anti-PD-1, Anti-CTLA-4

Disqualifiers: Local therapy candidates, Serious disorders, 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: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new immunotherapy combination works better than standard chemotherapy for treating bladder cancer that cannot be surgically removed or has metastasized. Participants will receive either a combination of two immunotherapy drugs, nivolumab and ipilimumab, or standard chemotherapy drugs such as carboplatin, cisplatin, or gemcitabine. The trial aims to determine which treatment is more effective. Ideal participants have metastatic or inoperable bladder cancer and have not previously received systemic chemotherapy for this condition. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

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 the combination of nivolumab and ipilimumab is generally well-tolerated by patients with advanced bladder cancer. One study found the most common immune-related side effects included skin rash in 16% of patients, diarrhea or bowel inflammation in 6%, and liver inflammation in 3%. Additionally, the FDA has already approved nivolumab, part of this combination, for treating certain urinary tract cancers, indicating a known safety profile.

The chemotherapy drugs carboplatin, cisplatin, and gemcitabine have been standard treatments for many years. They are generally effective, but side effects can include nausea, tiredness, and a decrease in blood cells, which may increase infection risk.

Overall, while both treatment options have side effects, the immunotherapy combination has shown promising results with a known safety profile in earlier studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the investigational immunotherapy treatments for bladder cancer because they involve the combination of Ipilimumab and Nivolumab, which work by supercharging the body's immune system to fight cancer cells. Unlike standard chemotherapy options like Carboplatin, Cisplatin, and Gemcitabine, which directly attack cancer cells, these immunotherapies target specific immune checkpoints, potentially leading to more precise and long-lasting responses. This unique mechanism of action could offer a promising alternative for patients, potentially reducing side effects and improving outcomes compared to traditional chemotherapy.

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

Research has shown that using nivolumab and ipilimumab together may help treat advanced bladder cancer. In this trial, some participants will receive this investigational immunotherapy combination. Studies have found that this combination can improve outcomes for patients with metastatic urothelial carcinoma, a type of bladder cancer that has spread. Patients receiving these two drugs have experienced benefits, even when other treatments have failed. Research also suggests that this combination can be effective for different types of tumors, including bladder cancer. Early results indicate that these drugs may help patients who haven't responded to other treatments. ^{5 6 7 8 9}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for adults with untreated inoperable or metastatic bladder cancer. Participants should be relatively fit (ECOG status 0 or 1), have not had chemotherapy for this condition, and must agree to use contraception if applicable. Those with serious medical issues, previous treatments targeting immune checkpoints, or who are candidates for curative local therapy cannot join.

Inclusion Criteria

To learn more about participating in a clinical trial with Bristol-Myers Squibb, please visit www.BMSStudyConnect.com.

My cancer, which started in the urinary system, cannot be removed by surgery.

I agree to use birth control as required.

Exclusion Criteria

Any serious or uncontrolled medical disorder in the opinion of the investigator that may increase the risk associated with study participation or study drug administration or interfere with the interpretation of study results

I have previously received treatments targeting immune checkpoints.

My condition can be treated with the goal of curing it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either investigational immunotherapy (nivolumab with ipilimumab) or standard of care chemotherapy

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Gemcitabine
• Ipilimumab
• Nivolumab

Trial Overview The study tests the effectiveness of Nivolumab combined with Ipilimumab or standard chemotherapy (Gemcitabine plus Cisplatin/Carboplatin) against standard chemotherapy alone in treating advanced bladder cancer. The goal is to see which treatment helps more.

How Is the Trial Designed?

Group I: Arm C: Investigational immunotherapy Experimental Treatment 3 Interventions

Group II: Arm A: Investigational immunotherapy Experimental Treatment 2 Interventions

Group III: Arm B: Standard of care chemotherapy Active Control 3 Interventions

Group IV: Arm D: Standard of care chemotherapy Active Control 2 Interventions

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Ono Pharmaceutical Co. Ltd

Industry Sponsor

Trials

182

Recruited

97,100+

Shinji Takai

Ono Pharmaceutical Co. Ltd

Chief Medical Officer since 2023

MD from an unspecified institution

Gyo Sagara

Ono Pharmaceutical Co. Ltd

Chief Executive Officer since 2024

PhD in Pharmaceutical Sciences from Kyoto University

Published Research Related to This Trial

The combination of gemcitabine and carboplatin shows a promising overall response rate of 60% in treating transitional cell carcinoma of the bladder, making it a potential alternative for patients who cannot tolerate cisplatin due to renal impairment or other comorbidities.

Given the high chemosensitivity of transitional cell carcinoma, this new treatment combination warrants further investigation in future phase III trials to confirm its efficacy and safety in a broader patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine/carboplatin in advanced urothelial cancer. Carles, J., Nogué, M.[2022]

In a study of 140 patients with non-metastatic muscle-invasive bladder cancer, both gemcitabine plus cisplatin (Gem/Cis) and gemcitabine plus carboplatin (Gem/Carbo) regimens showed similar rates of complete clinical response (cCR) before surgery, indicating that both treatments are effective in this context.

However, patients receiving Gem/Cis had significantly better overall survival (OS) compared to those on Gem/Carbo, with median OS of 41 months versus 26 months, suggesting that while both regimens are effective, Gem/Cis may offer a survival advantage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncological Outcomes of Neoadjuvant Gemcitabine plus Carboplatin versus Gemcitabine plus Cisplatin in Locally Advanced Bladder Cancer: A Retrospective Analysis. Mofid, B., Razzaghdoust, A., Ghajari, M., et al.[2022]

In a phase II study involving 27 patients with advanced transitional cell carcinoma, the sequential treatment of gemcitabine and carboplatin followed by paclitaxel resulted in an objective response rate of 40.7%, with one complete response and ten partial responses.

The treatment was generally safe, with hematologic toxicities being the most common, but the study concluded that while this sequential approach appears safer than triplet therapy, it did not significantly improve patient outcomes, indicating a need for further research with larger groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential therapy with gemcitabine and Carboplatin followed by Paclitaxel as first line treatment for advanced urothelial cancer. Kattan, JG., Boutros, CY., Farhat, FS., et al.[2021]

Cisplatin is a key treatment for bladder cancer, but managing its side effects, like nausea and acute kidney injury, is crucial to maintain treatment effectiveness and avoid dose reductions.

An effective strategy for preventing cisplatin-associated nausea and vomiting involves a four-drug prophylactic regimen, while intensive hydration is essential for preventing acute kidney injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of cisplatin-associated toxicities in bladder cancer patients. Desilets, A., Adam, JP., Soulières, D.[2021]

In a multicenter study involving 48 patients with metastatic transitional cell carcinoma, Carboplatin, a less toxic analogue of Cisplatin, showed minimal activity with no complete remissions and only 3 partial responses.

The study indicates that Carboplatin may not be an effective treatment option for bladder cancer, especially since 30 of the patients had not previously undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of carboplatin in metastatic transitional cell carcinoma of the bladder (a report of the Medical Research Council Working Party on Urological Cancer, Subgroup in Advanced Bladder Cancer). [2013]

The gemcitabine and carboplatin combination treatment for advanced transitional cell carcinoma (TCC) showed a 56.1% overall response rate, making it an effective alternative to standard cisplatin-based therapies, especially for patients with impaired renal function or poor performance status.

Despite significant hematologic toxicities, such as neutropenia and anemia, the treatment had an acceptable safety profile, allowing for administration in elderly patients and those with other health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and carboplatin in advanced transitional cell carcinoma of the urinary tract: an alternative therapy. Nogué-Aliguer, M., Carles, J., Arrivi, A., 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]

Citations

1. opdivo.com opdivo.com/bladder-urinary-tract-cancer/clinical-trial-results/advanced-untreated-immunotherapy-chemo

Clinical trial results for advanced bladder or urinary tract ... See how OPDIVO® (nivolumab) plus chemotherapy performed in a clinical trial as a treatment for certain adults with advanced bladder or urinary tract cancer, ...

2. opdivohcp.com opdivohcp.com/efficacy/uc

Efficacy Data for Urothelial Carcinoma (UC) - Opdivo In Checkmate 8HW, serious adverse reactions occurred in 46% of patients receiving OPDIVO in combination with ipilimumab. The most frequent serious adverse ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11082753/

Nivolumab + Ipilimumab as Immunotherapeutic Boost in ... These findings suggest that second-/third-line nivolumab plus high-dose ipilimumab may benefit patients with metastatic urothelial carcinoma.

4. news.bms.com news.bms.com/news/details/2018/Opdivo-nivolumab-in-Combination-with-Yervoy-ipilimumab-Shows-Promising-Results-in-Patients-with-Advanced-Form-of-Bladder-Cancer/default.aspx

Opdivo (nivolumab) in Combination with Yervoy ... “The combination of Opdivo and Yervoy has shown durable efficacy across a broad range of tumor types and treatment settings, and we are equally ...

5. cancernetwork.com cancernetwork.com/view/nivolumab-ipilimumab-shows-improved-benefit-in-urothelial-carcinoma

Nivolumab/Ipilimumab Shows Improved Benefit in ... Nivolumab plus ipilimumab has shown a response benefit when given at an increased dose for those with metastatic urothelial carcinoma.

6. news.bms.com news.bms.com/news/details/2016/Opdivo-nivolumab-and-Yervoy-ipilimumab-Regimen-Shows-Promising-Efficacy-and-Safety-in-Previously-Treated-Patients-With-Advanced-Form-of-Bladder-Cancer/default.aspx

Opdivo (nivolumab) and Yervoy (ipilimumab) Regimen ... Data from CheckMate -032 showed a confirmed objective response rate of 38.5% in previously treated metastatic urothelial carcinoma patients who received the ...

7. opdivo.com opdivo.com/bladder-urinary-tract-cancer/clinical-trial-results/advanced-previously-treated-immunotherapy

Previously Treated Advanced Bladder or Urinary Tract ... 7 out of 270 people, or 3%, saw tumors disappear completely in response to OPDIVO® for previously treated advanced bladder cancer.

8. opdivo.com opdivo.com/bladder-urinary-tract-cancer

Bladder or Urinary Tract (Urothelial) Cancer Treatment OPDIVO® (nivolumab) is an FDA-approved immunotherapy that can be used alone, or with chemotherapy, to treat three different types of urinary tract cancer ...

9. opdivohcp.com opdivohcp.com/dosing/uc

Urothelial Carcinoma Dosing Schedules - Opdivo The most common immune-mediated adverse reactions were rash (16%), diarrhea/colitis (6%), and hepatitis (3%). In Checkmate 816, the most common (>20%) adverse ...