Chemotherapy + Nivolumab for Bladder Cancer

Not currently recruiting at 390 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

Disqualifiers: Metastatic bladder cancer, others

Stay on Your Current Meds You can continue your current medications while participating

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with previously untreated muscle-invasive bladder cancer. It compares the effects of adding nivolumab, an immunotherapy drug that aids the immune system in fighting cancer, to standard chemotherapy (gemcitabine and cisplatin) before surgery. Participants will receive either standard chemotherapy alone or chemotherapy with nivolumab to determine which option is more effective. Eligible participants are those with muscle-invasive bladder cancer who have not undergone prior treatments such as systemic therapy or radiation. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity 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?

Studies have shown that combining nivolumab with gemcitabine and cisplatin (GC chemotherapy) can lead to serious side effects. In one study, about 62% of patients experienced major side effects, such as extreme tiredness or low blood cell counts. Another study reported that around 52% of patients faced similar severe side effects.

Nivolumab, when used with GC chemotherapy, has already received approval for treating some other cancers. This indicates extensive research and a substantial understanding of its safety. However, despite its potential effectiveness, this treatment carries a high risk of serious side effects. Patients should consult their healthcare provider to determine if this treatment is suitable for them. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bladder cancer?

Researchers are excited about combining Nivolumab with chemotherapy for bladder cancer because it introduces a new mechanism of action. Most treatments for bladder cancer, like the standard chemotherapy drugs Cisplatin and Gemcitabine, work by directly killing cancer cells. However, Nivolumab is an immunotherapy that targets the PD-1 pathway, helping the immune system recognize and attack cancer cells more effectively. This dual approach could potentially enhance treatment effectiveness and provide new hope for patients by boosting the body’s own defenses against cancer.

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

This trial will compare two treatment approaches for muscle-invasive bladder cancer. In Arm A, participants will receive Gemcitabine and Cisplatin (GC) chemotherapy. In Arm B, participants will receive Nivolumab combined with GC chemotherapy. Research has shown that combining Nivolumab with GC chemotherapy can effectively treat muscle-invasive bladder cancer. One study found that patients receiving this combination had a complete response lasting about 37 months on average, compared to 13 months for those receiving only GC chemotherapy. Another study found that more than 40% of patients responded well to cisplatin-based chemotherapy, with a median overall survival of around 15 months. Adding Nivolumab to this combination has shown significant improvements in survival. Overall, these findings suggest that including Nivolumab with GC chemotherapy could enhance the effectiveness of bladder cancer treatment. ^{1 2 6 7 8}

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 muscle-invasive bladder cancer who haven't had previous systemic therapy, radiation, or surgery (except certain biopsies and tumor resections). They must be fit enough for surgery as assessed by their doctors and have a performance status showing they can handle daily activities with ease or minor limitations.

Inclusion Criteria

I am approved for and agree to have bladder removal surgery after initial treatment.

I am fully active or can carry out light work.

Exclusion Criteria

My cancer has spread to my lymph nodes or is metastatic bladder cancer.

I have only had TURBT or biopsies for my bladder cancer, no other treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive neoadjuvant gemcitabine/cisplatin (GC) chemotherapy, with or without nivolumab

12 weeks

Surgery

Participants undergo surgery for muscle-invasive bladder cancer

1 week

Post-Surgery Therapy

Participants receive continued immuno-oncology therapy with nivolumab or nivolumab and BMS-986205

43 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 months

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Gemcitabine
• Nivolumab

Trial Overview The study compares two approaches: one group receives chemotherapy drugs gemcitabine/cisplatin alone, while the other gets these chemo drugs plus Nivolumab. After surgery to remove the bladder, some participants will continue treatment with Nivolumab or Nivolumab combined with BMS-986205.

How Is the Trial Designed?

Group I: Arm B: Nivolumab + GC Chemotherapy Experimental Treatment 3 Interventions

Group II: Arm A: Gemcitabine/Cisplatin (GC) Chemotherapy Active Control 2 Interventions

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

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

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 sequential treatment of gemcitabine and cisplatin followed by docetaxel showed a promising objective response rate of 55.2% in 38 patients with advanced urothelial carcinoma, indicating its efficacy as a first-line therapy.

The treatment was generally well tolerated, with manageable side effects; although 27% experienced severe neutropenia during the GP regimen, there were no toxic deaths reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential gemcitabine and cisplatin followed by docetaxel as first-line treatment of advanced urothelial carcinoma: a multicenter phase II study of the Hellenic Oncology Research Group. Boukovinas, I., Androulakis, N., Vamvakas, L., et al.[2022]

The gemcitabine and cisplatin doublet regimen has shown a better efficacy-toxicity profile compared to the traditional MVAC chemotherapy for bladder cancer, making it a more suitable option for elderly patients with metastatic disease.

Ongoing phase II studies of triplet regimens combining gemcitabine, paclitaxel, and either cisplatin or carboplatin have demonstrated promising activity and improved median survival, particularly in patients with visceral disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of gemcitabine triplets in metastatic bladder cancer. de Wit, R., Bellmunt, J.[2022]

Gemcitabine, a newer chemotherapy agent, has shown promising activity against bladder cancer, both as a single agent and in combination with cisplatin, offering a favorable toxicity profile compared to traditional treatments.

The standard treatment for advanced bladder cancer in the US remains the M-VAC regimen, but ongoing trials are exploring the effectiveness of gemcitabine combined with other agents, which may lead to improved treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in the treatment of bladder cancer. Ryan, CW., Vogelzang, NJ.[2022]

In a phase III trial with 405 patients, the gemcitabine/cisplatin (GC) regimen showed comparable effectiveness to the standard MVAC regimen for advanced bladder cancer, with similar response rates and overall survival.

The GC regimen demonstrated significantly better safety and tolerability, with much lower rates of severe side effects like mucositis and neutropenic fever, suggesting it should be preferred as the standard treatment for advanced bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in advanced bladder cancer. von der Maase, H.[2022]

In a study of 11 patients with untreated metastatic bladder cancer, cis-diamminedichloroplatinum (CDDP) showed a partial response in 37.5% of patients, indicating some efficacy in this difficult-to-treat population.

While CDDP was generally tolerated, it caused moderate nausea and vomiting in some patients, and nephrotoxicity was a significant concern, leading to renal failure in 2 patients with ureteral obstruction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cis-diamminedichloroplatinum activity in bidimensionally measurable metastatic lesions of bladder carcinoma. De Lena, M., Lorusso, V., Iacobellis, U., 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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2309863

Nivolumab plus Gemcitabine–Cisplatin in Advanced ... First-line cisplatin-based chemotherapy has shown a response in more than 40% of patients, with a median overall survival of approximately 15 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37870949/

Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial ... The median duration of complete response was 37.1 months with nivolumab-combination therapy and 13.2 months with gemcitabine-cisplatin alone.

3. nature.com nature.com/articles/s41591-023-02568-1

Gemcitabine and cisplatin plus nivolumab as organ- ... Our study demonstrates that stringently defined cCR is associated with favorable survival outcomes and that prolonged bladder-intact survival is ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666634023004014

Gemcitabine with cisplatin and nivolumab: Redefining ... About 22% achieved complete response with the addition of nivolumab, with median duration of complete response being 37 months. Grade 3 or ...

5. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-combination-cisplatin-and-gemcitabine-unresectable-or-metastatic-urothelial

FDA approves nivolumab in combination with cisplatin and ... Statistically significant benefits in both OS and PFS were demonstrated for nivolumab in combination with cisplatin and gemcitabine followed by ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03558087

NCT03558087 | Gemcitabine, Cisplatin, Plus Nivolumab in ... This is a phase 2 trial seeking to define the safety and activity of gemcitabine, cisplatin, plus nivolumab as neoadjuvant therapy in patients with ...

7. urotoday.com urotoday.com/conference-highlights/aua-2024/aua-2024-bladder-cancer/151783-aua-2024-nivolumab-plus-gemcitabine-cisplatin-vs-gemcitabine-cisplatin-alone-in-patients-with-previously-untreated-unresectable-or-metastatic-urothelial-carcinoma-results-of-analyses-to-characterize-benefit-in-responders-from-the-checkmate-901-trial.html

AUA 2024: Nivolumab plus Gemcitabine-Cisplatin vs ... The primary tumor site was the bladder in 75% of patients in the NIVO+GC arm and 71% in the GC arm. Additionally, 38% of patients had high tumor ...

8. news.bms.com news.bms.com/news/details/2024/U.S.-Food-and-Drug-Administration-Approves-Opdivo--nivolumab-in-Combination-with-Cisplatin-and-Gemcitabine-for-First-Line-Treatment-of-Adult-Patients-with-Unresectable-or-Metastatic-Urothelial-Carcinoma/default.aspx

U.S. Food and Drug Administration Approves Opdivo ... Patients receiving Opdivo in combination with cisplatin and gemcitabine had their risk of disease progression or death reduced by 28%, with a ...