Nivolumab + Urelumab for Bladder Cancer

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

15 Participants Needed

Trial Summary

What is the purpose of this trial?

This study evaluates the post cystectomy CD8+ tumor response of patients receiving Nivolumab plus Urelumab versus Nivolumab alone. Half the patients will receive Nivolumab plus Urelumab, while the other half will receive Nivolumab alone.

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.

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

Research shows that Nivolumab, a part of the treatment, has been effective in prolonging disease-free survival in patients with muscle-invasive urothelial carcinoma, a type of bladder cancer. Additionally, similar drugs that target the same pathway as Nivolumab have shown favorable clinical activity and tolerability in patients with advanced bladder cancer. ^{1 2 3 4 5}

How is the drug combination of Nivolumab and Urelumab unique for treating bladder cancer?

The combination of Nivolumab and Urelumab is unique because it combines two types of immune checkpoint inhibitors, targeting different pathways to enhance the immune system's ability to fight bladder cancer. Nivolumab blocks the PD-1 pathway, while Urelumab targets the 4-1BB pathway, potentially offering a more robust immune response compared to treatments that target only one pathway. ^{1 2 3 5 6}

Research Team

Noah Hahn, M.D.

Principal Investigator

Johns Hopkins University

Eligibility Criteria

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

I am 18 years old or older.

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.

Exclusion Criteria

My cancer is advanced and cannot be removed by surgery.

I have cancer in the upper part of my urinary system.

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

Timeline

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

Treatment Details

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.

Participant Groups

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

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]

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]

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]

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 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]

References

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

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

2. United States 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. [2022]

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

PD-L1 Expression in Urothelial Carcinoma With Predominant or Pure Variant Histology: Concordance Among 3 Commonly Used and Commercially Available Antibodies. [2021]

4. Netherlands 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. [2023]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

Clinicopathologic and Genomic Characterization of PD-L1 Positive Urothelial Carcinomas. [2021]