Nivolumab for Bladder Cancer

(NEXT Trial)

Not currently recruiting at 1 trial location

Overseen By Susan Sharry

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Utah

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Metastases, Autoimmune disease, Immunocompromised, 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)

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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how effectively the drug Nivolumab (Opdivo) prevents bladder cancer from returning two years after treatment. It targets individuals with bladder cancer that has invaded the muscle but has not spread to other parts of the body, and who are unable to have their bladder removed for various reasons. Participants should have already completed a combination of chemotherapy and radiation. The study seeks to provide a new option for those unable to undergo major surgery, with a focus on improving survival rates without cancer recurrence. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

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 14 days before starting the study drug.

Is there any evidence suggesting that nivolumab is likely to be safe for humans?

Research has shown that nivolumab is generally well-tolerated by patients with bladder cancer. The FDA has already approved it for treating some urinary tract cancers. Studies have found that the most common side effects include tiredness, muscle pain, nausea, and loss of appetite, reported by at least 20% of patients. Although these effects are common, they can usually be managed. This evidence suggests that nivolumab is relatively safe for treating bladder cancer. ^{1 2 3 4 5}

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

Nivolumab is unique because it harnesses the power of the immune system to fight bladder cancer. Unlike traditional treatments like chemotherapy and surgery, which directly target cancer cells, nivolumab works by blocking a protein called PD-1. This action unleashes the immune system to recognize and attack cancer cells more effectively. Researchers are excited about nivolumab because it offers a targeted approach that may lead to fewer side effects and more durable responses in patients.

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

Research has shown that nivolumab can be effective for people with certain types of cancer. For those with cancer in the upper part of the urinary tract, 73.1% of patients remained disease-free after 2 years, and 85.1% survived. In bladder cancer, patients who received nivolumab had a 30% lower chance of cancer recurrence after surgery. This treatment enhances the immune system's ability to detect and combat cancer cells. In this trial, all participants will receive nivolumab, which might benefit individuals with localized bladder cancer who have undergone chemoradiation. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Adults with localized muscle-invasive bladder cancer stages T2-4b, N0/N+, M0 or T1 with N+ who've had chemoradiation and can't have radical cystectomy. Must be ≥18 years old, ECOG ≤2, adequate organ function, no distant metastases/active malignancies/autoimmune diseases/HIV/hepatitis. Women must not be pregnant and agree to contraception.

Inclusion Criteria

I had surgery to remove part of my bladder due to cancer before starting chemoradiation.

My cancer originates from the bladder, urethra, or lower ureter.

I am using two birth control methods or am not able to have children, and will continue for 5 months after the study.

Exclusion Criteria

You have a known or suspected autoimmune disease that is currently active.

I haven't taken high-dose steroids or other immune-weakening drugs in the last 14 days.

My cancer has spread to areas not treated by radiation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiation

Participants undergo chemoradiation for localized bladder cancer

6-8 weeks

Adjuvant Nivolumab Treatment

Participants receive adjuvant nivolumab following chemoradiation

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Long-term Follow-up

Evaluate overall survival up to 5 years

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab

Trial Overview This phase 2 trial tests if the drug Nivolumab improves failure-free survival over two years in adults after chemoradiation for bladder cancer. It's a single-arm study where all participants receive the same treatment without comparison to a placebo or other therapy.

How Is the Trial Designed?

Group I: Nivolumab, all patients Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Bristol-Myers Squibb

Industry 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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1078143925002662

Efficacy of adjuvant nivolumab in patients with upper tract ... 24-month disease-free survival (DFS) reached 73.1%, and overall survival (OS) to 85.1% in upper tract urothelial carcinoma (UTUC) group. •.

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

Efficacy Data for Urothelial Carcinoma (UC) - Opdivo In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated rash occurred in 16% (108/666) of patients, including Grade 3 (3.5%) and ...

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

Clinical Outcomes in Patients With Muscle-Invasive Urothelial ... This cohort study examines treatment patterns and clinical outcomes for patients with muscle-invasive urothelial carcinoma treated with adjuvant nivolumab.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.658

Adjuvant nivolumab (NIVO) vs placebo (PBO) for high-risk ... Adjuvant NIVO demonstrated statistically significant and clinically meaningful disease-free survival (DFS) benefit vs PBO in pts with high-risk MIUC after ...

5. 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.

6. 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 ...

7. fda.gov fda.gov/drugs/resources-information-approved-drugs/nivolumab-treatment-urothelial-carcinoma

Nivolumab for Treatment of Urothelial Carcinoma The most common adverse reactions (reported in at least 20% of patients) were fatigue, musculoskeletal pain, nausea, and decreased appetite.

8. 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 ...

9. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK602620/

Nivolumab (Opdivo) - NCBI Bookshelf - NIH Evidence from a clinical trial demonstrated that patients treated with Opdivo experienced a delay until their cancer returned. Opdivo meets the needs of ...

10. 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.