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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests nivolumab, an immunotherapy drug, for people with bladder cancer that has spread. It targets patients whose tumors have specific genetic changes (ARID1A mutation) and examines how these changes interact with the immune system. The goal is to determine if nivolumab can control the cancer by enhancing the immune system's ability to fight it. Patients with these genetic changes who have experienced disease progression after chemotherapy might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that nivolumab is a well-tolerated treatment for cancer patients. It is already a standard treatment for certain types of bladder cancer and has reduced the risk of cancer returning after surgery by 30%. This indicates it is generally safe for humans.

When combined with relatlimab, research shows more reports of side effects compared to nivolumab alone, but these do not significantly increase safety concerns. Studies with advanced lung cancer patients found that adding relatlimab did not raise toxicity levels, indicating a similar safety profile.

Overall, while some side effects exist, both nivolumab and its combination with relatlimab have been manageable and do not pose major safety issues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about nivolumab for bladder cancer because it works differently than standard treatments. Unlike traditional therapies like chemotherapy, which target rapidly dividing cells indiscriminately, nivolumab is an immunotherapy that enhances the body's immune system to specifically attack cancer cells. It blocks a protein called PD-1, a mechanism that cancer cells exploit to hide from immune detection. By combining nivolumab with relatlimab, which targets another immune checkpoint called LAG-3, this treatment offers a dual mechanism that could potentially lead to more effective and longer-lasting responses.

What evidence suggests that nivolumab might be an effective treatment for metastatic urothelial cancer?

Research has shown that combining nivolumab with relatlimab may help treat certain cancers. This trial will evaluate the effectiveness of this combination for metastatic urothelial cancer. In advanced melanoma, this combination helped patients live longer without cancer progression, with an average survival time of 51 months. In advanced lung cancer, adding relatlimab to nivolumab increased treatment effectiveness without additional safety issues. These findings suggest that this drug combination might enhance the immune system's ability to fight metastatic urothelial cancer, particularly in patients with specific genetic changes. ^{6 7 8 9 10}

Who Is on the Research Team?

Sangeeta Goswami

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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 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]

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]

Citations

1. targetedonc.com targetedonc.com/view/relatlimab-and-nivolumab-deliver-durable-survival-and-suggests-biomarker-in-resectable-melanoma?utm_source=www.targetedonc.com&utm_medium=relatedContent

Neoadjuvant Relatlimab/Nivolumab Combo Shows ... Investigators reported that recurrence-free survival (RFS) at 4 years was 95% for major pathologic response (MPR) vs 60% for those who did not ( ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39671533/

Three-Year Overall Survival With Nivolumab Plus ... Nivolumab plus relatlimab demonstrated a statistically significant improvement in progression-free survival (PFS), along with a clinically ...

3. oncnursingnews.com oncnursingnews.com/view/adding-relatlimab-to-nivolumab-chemo-did-not-increase-toxicity

Adding Relatlimab to Nivolumab/Chemo Did Not Increase ... Adding relatlimab to nivolumab and chemotherapy improved efficacy but did not increase safety concerns in advanced-stage lung cancer.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT07079644

Outcomes of Nivolumab in Combination With Relatlimab ... Outcomes of Nivolumab in Combination With Relatlimab in Patients With Advanced Melanoma in the Flatiron Database. ClinicalTrials.gov ID NCT07079644. Sponsor ...

5. cancernetwork.com cancernetwork.com/view/nivolumab-relatlimab-shows-sustained-efficacy-in-advanced-melanoma

Nivolumab/Relatlimab Shows Sustained Efficacy in ... Data showed a median overall survival (OS) of 51.0 months (95% CI, 34.0-not reached [NR]) in the nivolumab/relatlimab arm and 34.1 months (95% ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00340

Adjuvant Nivolumab in High-Risk Muscle-Invasive ... The current OS data show a 24% reduction in the risk of death for patients treated with nivolumab in the ITT population and a 44% reduction for ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12150186/

Clinical Outcomes in Patients With Muscle-Invasive Urothelial ... Nivolumab is a standard-of-care adjuvant therapy for patients with muscle-invasive urothelial carcinoma (MIUC) at high risk for recurrence after ...

8. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-bladder-cancer/158278-asco-gu-2025-adjuvant-nivolumab-vs-placebo-for-high-risk-muscle-invasive-urothelial-carcinoma-additional-efficacy-outcomes-including-overall-survival-in-patients-with-mibc-from-checkmate-274.html

ASCO GU 2025: Adjuvant Nivolumab vs Placebo for High- ... The primary endpoints were disease free survival in ITT and tumor PD-L1 expression ≥ 1% patients. Overall survival in ITT and PD-L1 ≥ 1% ...

9. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK601741/

Clinical Review - Nivolumab (Opdivo) - NCBI Bookshelf - NIH The 5-year survival among patients with localized muscle-invasive urothelial carcinoma (MIUC) is approximately 40% to 50%.

10. opdivo.com opdivo.com/bladder-urinary-tract-cancer/clinical-trial-results/after-surgery-immunotherapy

Clinical trial results for bladder or urinary tract cancer after ... People given OPDIVO had a 30% lower risk of their cancer returning after surgery than those given placebo.