Nivolumab + Urelumab for Bladder Cancer

Not currently recruiting at 4 trial locations

Overseen By Noah Hahn, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Immune checkpoint inhibitors

Disqualifiers: Metastatic cancer, Second malignancy, Transplant, Hepatitis, 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

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of two medications, Nivolumab and Urelumab, for bladder cancer patients who have undergone bladder removal surgery. Researchers aim to determine if combining these drugs is more effective than using Nivolumab alone by focusing on the body's CD8+ tumor response, a part of the immune system that fights cancer. The trial includes two groups: one receives both drugs, while the other receives only Nivolumab. This study suits those who cannot or choose not to take certain chemotherapy drugs and have stable health conditions that do not interfere with the trial. As a Phase 2 trial, the research focuses on measuring 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, it mentions that patients who have received certain cancer therapies or radiotherapy within 4 weeks prior to starting the study drug are excluded. It's best to discuss your specific medications with the study team.

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

Research has shown that using Nivolumab and Urelumab together has been tested in cancer patients with encouraging safety results. Studies have examined this combination in individuals with advanced solid tumors. Although higher doses of Urelumab raised concerns about liver inflammation, lower doses have proven much safer.

Nivolumab alone is well-known for treating various cancers and is generally well-tolerated. Combining it with Urelumab has not revealed any unexpected safety issues, except for the need to monitor liver health closely. Most patients can safely receive this treatment combination, but doctors will monitor liver function to prevent serious side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Nivolumab and Urelumab for bladder cancer because it offers a fresh approach to treatment. Unlike standard options like chemotherapy, which targets rapidly dividing cells, Nivolumab is an immunotherapy that helps the immune system recognize and attack cancer cells. Urelumab further enhances this effect by activating a specific immune pathway called CD137. This dual action boosts the body’s natural defenses against cancer, potentially leading to more effective and durable responses.

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

Research has shown that using Nivolumab with Urelumab may help treat advanced solid tumors. In this trial, participants will receive either Nivolumab alone or in combination with Urelumab. Nivolumab helps the immune system target cancer cells, and early results indicate its effectiveness in treating bladder cancer. Adding Urelumab, which boosts immune activity, might enhance these effects. Previous studies with this combination have shown promising results in advanced cancers, suggesting a stronger attack on tumors. This combination could offer new hope for patients with bladder cancer. ^{1 4 5 6 7}

Who Is on the Research Team?

Noah Hahn, M.D.

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with muscle-invasive bladder cancer who can't or won't take cisplatin-based chemo. They must understand the study and agree to its terms, have certain blood counts (ANC ≥ 1.5 K/mm3, Platelets ≥ 100 K/mm3, Hgb ≥ 9 g/dL), liver function within limits, and a creatinine clearance of at least 30 mL/min. Pregnant women, those not using effective contraception, and patients with recent major surgery or other severe conditions are excluded.

Inclusion Criteria

Patients who give a written informed consent obtained according to local guidelines

I am not taking cisplatin-based chemotherapy before surgery by choice or because I'm not eligible.

You must have certain levels of white blood cells, platelets, hemoglobin, bilirubin, and liver enzymes in your blood, and a certain level of kidney function.

Exclusion Criteria

My cancer is advanced and cannot be removed by surgery.

I have recently received treatment for cancer, including immunotherapy or radiation.

I am not using two highly effective birth control methods.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nivolumab with or without Urelumab for two cycles

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Urelumab

Trial Overview The trial tests how well Nivolumab works alone versus combined with Urelumab in shrinking bladder cancer before surgery. Patients are split into two groups: one receives both drugs while the other gets only Nivolumab.

How Is the Trial Designed?

Group I: Nivolumab in combination with Urelumab Experimental Treatment 1 Intervention

Nivolumab and Urelumab combination: Nivolumab 240 mg will be administered by 1 hour intravenous infusion on day 1 and day 15 for two cycles Urelumab 8mg will be administered by 1 hour intravenous infusion on day 1 for two cycles

Group II: Nivolumab monotherapy Active Control 1 Intervention

Nivolumab 240 mg will be administered by 1 hour intravenous infusion on day 1 and day 15 for two cycles

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?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

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

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]

In a study of 528 urothelial carcinoma patients, 44.5% were found to be PD-L1 positive, with higher positivity rates in metastatic sites compared to primary tumors, indicating that the location of the tumor may influence PD-L1 expression.

Genomic profiling revealed that PD-L1 positive patients had more frequent alterations in TP53 and RB1, while PD-L1 negative patients had more FGFR3 alterations, suggesting distinct genomic characteristics that could help predict responses to immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinicopathologic and Genomic Characterization of PD-L1 Positive Urothelial Carcinomas. Huang, RSP., Haberberger, J., Harries, L., et al.[2021]

Durvalumab, a monoclonal antibody targeting PD-L1, showed a manageable safety profile in patients with advanced urothelial bladder cancer, with common side effects including fatigue and diarrhea, but no severe (grade 4 or 5) adverse events reported.

The treatment demonstrated a 31% overall response rate, with a significantly higher response of 46.4% in patients with PD-L1-positive tumors, indicating that PD-L1 expression may play a crucial role in the efficacy of durvalumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Durvalumab (MEDI4736), an Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer. Massard, C., Gordon, MS., Sharma, S., et al.[2022]

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 involving 709 patients with muscle-invasive urothelial carcinoma, nivolumab did not lead to any clinically meaningful deterioration in health-related quality of life (HRQoL) compared to placebo, indicating it is a safe treatment option.

Nivolumab was found to maintain HRQoL while also prolonging the time until cancer recurrence, demonstrating its efficacy in improving patient outcomes after radical resection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life with Adjuvant Nivolumab After Radical Resection for High-risk Muscle-invasive Urothelial Carcinoma: Results from the Phase 3 CheckMate 274 Trial. Witjes, JA., Galsky, MD., Gschwend, JE., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10921538/

Final results of urelumab, an anti-CD137 agonist monoclonal ... Here, we report two studies that evaluated urelumab in combination with cetuximab or nivolumab in patients with select, advanced solid tumors.

2. opdivo.com opdivo.com/bladder-urinary-tract-cancer/clinical-trial-results/advanced-untreated-immunotherapy-chemo

Clinical trial results for advanced bladder or urinary tract ... See how OPDIVO® (nivolumab) plus chemotherapy performed in a clinical trial as a treatment for certain adults with advanced bladder or urinary tract cancer, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02658981

Anti-LAG-3 Alone & in Combination w/ Nivolumab Treating ... This phase I trial studies the safety and best dose of anti-LAG-3 (anti-LAG-3 monoclonal antibody BMS-986016) or urelumab alone and in combination with ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7333812/

New emerging targets in cancer immunotherapy: CD137/4- ... Two agonist anti-CD137 mAb have been tested in the clinical setting; urelumab (BMS-663513), a fully human IgG4-based anti-CD137 mAb that does ...

5. delta.larvol.com delta.larvol.com/Products/?ProductId=ad86c464-1e1c-4c2d-b057-d411411c3d12

urelumab (BMS-663513) / BMS, Ono Pharma Phase-2 clinical trial testing intratumoral injections of the agonist anti-CD137 (4-1BB) mAb urelumab in combination with systemic nivolumab (CICON 2025) ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02658981

Anti-LAG-3 Alone & in Combination w/ Nivolumab Treating ... This phase I trial studies the safety and best dose of anti-LAG-3 (anti-LAG-3 monoclonal antibody BMS-986016) or urelumab alone and in combination with ...

7. ono-pharma.com ono-pharma.com/sites/default/files/en/news/press/sm_cn161118_1.pdf

Phase 1/2 Data Combining Urelumab with Opdivo ( ... Similar response was seen in both PD-L1 positive and PD-L1 negative melanoma patients, with ORR of 50% (10/20) and 47% (8/17) in those with >1% ...