Nivolumab for Bladder Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Active brain metastases, Autoimmune disease, HIV, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Up to 2 years

6 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the effect of nivolumab in urothelial cancer that has spread to other places in the body (metastatic), specifically in patients with aberrations in ARID1A gene (ARID1A mutation) and correlate with expression level of CXCL13, an immune cytokine. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving nivolumab may help control the disease in patients with urothelial cancer or solid tumors. This trial aims at enriching patient selection based on genomic and immunological attributes of the tumor.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them at least 14 days before starting the study drug.

What data supports the effectiveness of the drug Nivolumab for bladder cancer?

Nivolumab has shown effectiveness in treating metastatic urothelial carcinoma, especially after first-line platinum-based chemotherapy has failed, with an overall response rate of about 20%. It has been approved by the FDA for patients whose bladder cancer has progressed after platinum chemotherapy, indicating its potential to help patients with advanced stages of the disease. ^{1 2 3 4 5}

Is Nivolumab safe for treating bladder cancer?

Nivolumab, also known as Opdivo, is generally well tolerated in treating bladder cancer, with common side effects including tiredness, low white blood cell count, anemia (low red blood cell count), muscle pain, decreased appetite, and nausea. It has received FDA approval for use in patients with advanced bladder cancer who have not responded to platinum chemotherapy. ^{3 5 6 7 8}

How is the drug Nivolumab unique in treating bladder cancer?

Nivolumab is unique for bladder cancer treatment because it is an immunotherapy drug that works by blocking the PD-1 protein, helping the immune system attack cancer cells. It is used as a second-line treatment for patients whose cancer has progressed after platinum-based chemotherapy, offering a new option for those who cannot tolerate or do not respond to traditional chemotherapy. ^{2 3 4 5 9}

Research Team

Sangeeta Goswami

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with metastatic urothelial cancer and a specific genetic change (ARID1A mutation). Participants must have had prior treatment failure, be in good physical condition (ECOG PS 0 or 1), and have measurable disease. They cannot join if they've received certain immune therapies before, have active infections like hepatitis B/C, uncontrolled medical conditions, HIV/AIDS, untreated brain metastases, or are on high-dose steroids.

Inclusion Criteria

Your neutrophil count is at least 1500 per microliter within the last 7 days before starting the treatment.

Your platelet count is at least 100,000 per microliter of blood, as measured within 7 days before starting the study.

My tumor has an ARID1A mutation.

Exclusion Criteria

I haven't had cancer treatment or experimental therapy in the last 28 days.

Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)

I haven't had any active cancer in the last 3 years, except for certain curable types.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab and relatlimab intravenously on day 1 of each 28-day cycle for up to 2 years

Up to 2 years

1 visit every 4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

100 days, then every 3-6 months

Treatment Details

Interventions

• Nivolumab

Trial Overview The trial tests the effectiveness of Nivolumab—an immunotherapy drug—on patients whose cancer has spread and who show ARID1A mutations. It also examines how CXCL13 expression levels might influence responses to this treatment. The study includes diagnostic biomarker analysis to tailor therapy based on individual tumor characteristics.

Participant Groups

Group I: Treatment (nivolumab & relatlimab) Experimental Treatment 3 Interventions

Participants found to be eligible to take part in this study, you will receive nivolumab and relatlimab by vein over about 30 minutes on Day 1 of every 28-day study cycle (about every 4 weeks).

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

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

In a study of 86 patients with advanced/metastatic urothelial carcinoma, the combination of nivolumab and ipilimumab showed improved response rates, particularly in first-line treatment, with an objective response rate (ORR) of 45% compared to 27% in later lines of therapy.

Starting treatment with nivolumab alone was found to be inadequate for the aggressive nature of metastatic urothelial carcinoma, suggesting that dual checkpoint inhibition may be necessary for better outcomes in first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tailored Immunotherapy Approach With Nivolumab in Advanced Transitional Cell Carcinoma. Grimm, MO., Schmitz-Dräger, BJ., Zimmermann, U., et al.[2022]

Nivolumab, a monoclonal antibody that blocks PD-1, shows a 20% overall response rate in patients with metastatic urothelial carcinoma after failing first-line platinum-based chemotherapy, indicating its potential as a treatment option.

While nivolumab is associated with manageable toxicity, serious immune-related adverse events can occur, and current biomarkers like PD-1/PD-L1 expression are not reliable for predicting patient response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and its use in the second-line treatment of metastatic urothelial cancer. Raggi, D., Necchi, A., Giannatempo, P.[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]

In a phase 2 study involving 270 patients with metastatic urothelial carcinoma, nivolumab demonstrated a confirmed objective response rate of 19.6%, indicating it can provide meaningful clinical benefits even after previous treatments have failed.

The treatment was generally well-tolerated, with 18% of patients experiencing grade 3-4 adverse events, primarily fatigue and diarrhea, and only three treatment-related deaths, suggesting an acceptable safety profile for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Sharma, P., Retz, M., Siefker-Radtke, A., et al.[2022]

Nivolumab has received accelerated approval from the FDA for treating patients with locally advanced or metastatic urothelial carcinoma who have experienced disease progression after platinum chemotherapy.

This approval marks the second PD-1-targeting therapy approved for bladder cancer within a year, highlighting the growing options for patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Gets FDA Nod for Bladder Cancer. [2018]

In a study of 1,747 patients with advanced urothelial cancer, those who responded to anti-PD-1/L1 antibody treatment were more likely to experience adverse events of special interest (AESIs) and immune-mediated adverse events (imAEs), with 64% of responders reporting related AESIs compared to 34% of non-responders.

Patients with related AESIs had significantly improved overall survival, with a hazard ratio of 0.45, indicating that experiencing these adverse events may be associated with better treatment outcomes, regardless of the duration of exposure to the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of the Association Between Adverse Events and Outcome in Patients Receiving a Programmed Death Protein 1 or Programmed Death Ligand 1 Antibody. Maher, VE., Fernandes, LL., Weinstock, C., et al.[2020]

Thirteen clinical trials are currently investigating the use of immune checkpoint inhibitors as a treatment for high-risk non-muscle-invasive bladder cancer, particularly in patients who have not responded to Bacillus Calmette-Guérin (BCG) therapy.

Preliminary results from trials like SWOG S1605 and Keynote-057 indicate that checkpoint inhibitors, such as Pembrolizumab, show promising antitumor activity and are generally well-tolerated, suggesting they could be a viable alternative for patients with BCG-unresponsive bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoints inhibitors in the management of high-risk non-muscle-invasive bladder cancer. A scoping review. García-Perdomo, HA., Sánchez, AL., Spiess, PE.[2022]

Immunotherapy, particularly immune checkpoint inhibitors like atezolizumab and nivolumab, has received accelerated FDA approval for treating metastatic urothelial carcinoma, showing promise in improving patient outcomes.

The use of immunotherapy can lead to unique immune-related adverse events and response patterns, such as pseudoprogression, highlighting the need for careful management and the potential for predictive biomarkers to identify patients who will benefit most from these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in metastatic urothelial carcinoma: focus on immune checkpoint inhibition. Siefker-Radtke, A., Curti, B.[2021]

Immunotherapy using PD-1/PD-L1 checkpoint inhibitors has shown promising efficacy and safety in treating metastatic urothelial carcinoma, especially in patients who are refractory to platinum-based therapies or ineligible for cisplatin, as highlighted by various clinical trials.

While these therapies have demonstrated durable responses in some patients, there is currently no reliable method to predict which patients will benefit most from this treatment, indicating a need for better predictive tools and further research into optimal treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-Programmed Cell Death 1/Ligand 1 (PD-1/PD-L1) Antibodies for the Treatment of Urothelial Carcinoma: State of the Art and Future Development. Powles, T., Necchi, A., Rosen, G., et al.[2021]

References

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

Tailored Immunotherapy Approach With Nivolumab in Advanced Transitional Cell Carcinoma. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Nivolumab and its use in the second-line treatment of metastatic urothelial cancer. [2019]

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

[Immunotherapy for Bladder Cancer]. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. [2022]

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

Nivolumab Gets FDA Nod for Bladder Cancer. [2018]

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

Analysis of the Association Between Adverse Events and Outcome in Patients Receiving a Programmed Death Protein 1 or Programmed Death Ligand 1 Antibody. [2020]

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

Immune checkpoints inhibitors in the management of high-risk non-muscle-invasive bladder cancer. A scoping review. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Immunotherapy in metastatic urothelial carcinoma: focus on immune checkpoint inhibition. [2021]

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

Anti-Programmed Cell Death 1/Ligand 1 (PD-1/PD-L1) Antibodies for the Treatment of Urothelial Carcinoma: State of the Art and Future Development. [2021]