Immunotherapy Combo vs Chemotherapy for Bladder Cancer

(CheckMate901 Trial)

Recruiting at 329 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

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

1322 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine whether an investigational immunotherapy nivolumab in combination with ipilimumab or in combination with standard of care chemotherapy is more effective than standard of care chemotherapy alone in treating participants with previously untreated inoperable or metastatic urothelial cancer.

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.

What data supports the effectiveness of the drug combination of immunotherapy and chemotherapy for bladder cancer?

Research shows that immune checkpoint inhibitors, which are part of the immunotherapy drugs, have been effective in treating bladder cancer, especially for patients who cannot use cisplatin-based chemotherapy. These drugs help the immune system fight cancer and have been approved for use in patients who have progressed on cisplatin-based treatments or are ineligible for them. ^{1 2 3 4 5}

Is the combination of gemcitabine and carboplatin safe for treating bladder cancer?

Gemcitabine and carboplatin have been used together in treating bladder cancer, and while they can be effective, they also come with important side effects. Cisplatin, a similar drug, is known for its toxicities, and carboplatin is considered a less toxic alternative, but still requires careful management of side effects. ^{6 7 8 9 10}

How is the immunotherapy combo different from chemotherapy for bladder cancer?

The immunotherapy combo for bladder cancer, which includes drugs like Ipilimumab and Nivolumab, offers a novel approach by using the body's immune system to fight cancer, unlike traditional chemotherapy that directly targets cancer cells. This treatment is particularly beneficial for patients who cannot tolerate the toxicity of platinum-based chemotherapy, providing an alternative with potentially fewer side effects. ^{11 12 13 14 15}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

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]

References

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

[Immunotherapy for Bladder Cancer]. [2019]

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

Evolving Treatment of Advanced Urothelial Cancer. [2018]

3. Hungary pubmed.ncbi.nlm.nih.gov

[Immunotherapy in advanced urothelial cancer]. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Systemic chemotherapy in locally advanced and/or metastatic bladder cancer. [2007]

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

Treatment Approaches for Cisplatin-Ineligible Patients with Invasive Bladder Cancer. [2020]

6. Australia pubmed.ncbi.nlm.nih.gov

Sequential therapy with gemcitabine and Carboplatin followed by Paclitaxel as first line treatment for advanced urothelial cancer. [2021]

7. Iran pubmed.ncbi.nlm.nih.gov

Oncological Outcomes of Neoadjuvant Gemcitabine plus Carboplatin versus Gemcitabine plus Cisplatin in Locally Advanced Bladder Cancer: A Retrospective Analysis. [2022]

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

Management of cisplatin-associated toxicities in bladder cancer patients. [2021]

9. England 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]

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

Gemcitabine/carboplatin in advanced urothelial cancer. [2022]

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

Complete Response With Immunotherapy: A Case of Metastatic Bladder Cancer. [2021]

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

Paclitaxel in the treatment of advanced urothelial cancer. [2015]

13. England pubmed.ncbi.nlm.nih.gov

First-line immune checkpoint inhibitor use in cisplatin-eligible patients with advanced urothelial carcinoma: a secular trend analysis. [2020]

14. Netherlands pubmed.ncbi.nlm.nih.gov

Overall Survival of Patients Receiving Cisplatin or Carboplatin for Primary Metastatic Urothelial Carcinoma of the Bladder: A Contemporary Dutch Nationwide Cohort Study. [2022]

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

Gemcitabine and carboplatin in advanced transitional cell carcinoma of the urinary tract: an alternative therapy. [2022]