Nivolumab for Cancer Post-Surgery

(CheckMate 274 Trial)

Recruiting at 374 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Autoimmune disease, Prior malignancy, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Duration: 48 months

709 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the effectiveness and safety of Nivolumab compared to placebo in participants who have undergone radical surgery for invasive urothelial cancer.

Will I have to stop taking my current medications?

The trial requires that you stop taking corticosteroids or other immunosuppressive medications at least 14 days before starting the study drug.

What data supports the effectiveness of the drug Nivolumab for cancer post-surgery?

Nivolumab has shown effectiveness in treating advanced lung cancer and other solid cancers by improving survival rates and being well-tolerated compared to other treatments. It works by helping the immune system better recognize and attack cancer cells. ^{1 2 3 4 5}

Is Nivolumab generally safe for humans?

Nivolumab, also known as Opdivo, has been associated with some immune-related side effects like colitis (inflammation of the colon) and other adverse events such as fatigue, diarrhea, and rash. However, it is generally considered to have a manageable safety profile and is better tolerated than some other treatments, like docetaxel, in certain cancer patients. ^{6 7 8 9 10}

What makes the drug Nivolumab unique for cancer treatment after surgery?

Nivolumab is unique because it is a PD-1 inhibitor, which helps the immune system recognize and attack cancer cells, and it has shown significant benefits in improving survival rates in various cancers, including lung cancer, compared to traditional chemotherapy. It is administered intravenously and is generally better tolerated than some other treatments, making it a novel option for patients post-surgery. ^{1 2 3 4 8}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for patients who've had surgery to remove high-risk invasive urothelial cancer from the bladder, ureter, or renal pelvis. They should be currently free of disease (confirmed by imaging), have not received cisplatin chemotherapy before surgery unless ineligible or refusing further cisplatin treatment.

Inclusion Criteria

I can provide a sample of my tumor for testing.

I had a high-risk bladder, ureter, or kidney cancer.

I had major surgery to remove my bladder within the last 4 months.

Exclusion Criteria

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

Positive test for hepatitis B virus surface antigen (HBV s Ag) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection

Subjects with active, known or suspected autoimmune disease

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nivolumab or placebo following radical surgery for invasive urothelial cancer

48 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

53 months

Treatment Details

Interventions

• Nivolumab
• Placebo

Trial Overview The study is testing Nivolumab, an immunotherapy drug, against a placebo to see if it's more effective in preventing cancer recurrence after radical surgery. Participants will randomly receive either Nivolumab or a placebo without knowing which one they're getting.

Participant Groups

Group I: Nivolumab Experimental Treatment 1 Intervention

Nivolumab dose as specified

Group II: Placebo Placebo Group 1 Intervention

Placebo dose as specified

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?

Bristol-Myers Squibb

Lead 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

Ono Pharmaceutical Co. Ltd

Industry Sponsor

Trials

182

Recruited

97,100+

Shinji Takai

Ono Pharmaceutical Co. Ltd

Chief Medical Officer since 2023

MD from an unspecified institution

Gyo Sagara

Ono Pharmaceutical Co. Ltd

Chief Executive Officer since 2024

PhD in Pharmaceutical Sciences from Kyoto University

Findings from Research

Nivolumab, an anti-PD-1 antibody, was administered to a 63-year-old female patient with metastatic melanoma after renal transplantation, highlighting the potential for anti-tumor activity in high-risk patients, despite the challenges of concurrent immunosuppression.

The patient experienced acute renal allograft rejection and renal failure shortly after starting nivolumab, indicating significant risks associated with this treatment in transplant recipients, but she later showed a positive clinical response after re-challenging with nivolumab while on hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. Ong, M., Ibrahim, AM., Bourassa-Blanchette, S., et al.[2023]

Nivolumab, an immune checkpoint inhibitor, significantly improves overall survival and progression-free survival in patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CHECKMATE 017 study.

The safety and tolerability of nivolumab are favorable, and interestingly, the expression of the PD-L1 ligand does not predict treatment outcomes, suggesting that other factors may influence the effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. Lim, JS., Soo, RA.[2018]

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

Nivolumab, a PD-1 inhibitor, has demonstrated significant safety and efficacy in treating various advanced solid tumors, including melanoma and lung cancer, based on multiple high-level studies.

Future research should aim to identify predictive biomarkers for treatment response and explore the potential of combining nivolumab with other therapies, as well as determining the best treatment strategies and duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers. Wong, AC., Ma, B.[2018]

Nivolumab, an immunotherapy drug, can cause immune-mediated side effects like colitis, which may occur even after treatment has stopped.

Using higher doses of methylprednisolone led to a quicker resolution of symptoms in patients compared to previous cases, potentially reducing the need for hospitalization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and immune-mediated colitis. Walker, H., Brennan, P., Groome, M., et al.[2023]

Nivolumab significantly improved overall survival and progression-free survival in patients with unresectable or metastatic melanoma compared to dacarbazine, with hazard ratios of 0.42 and 0.43 respectively, based on a trial involving 418 patients.

The most common side effects of nivolumab included fatigue, diarrhea, and rash, but it was still considered to have a favorable benefit-risk profile compared to dacarbazine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma. Beaver, JA., Theoret, MR., Mushti, S., et al.[2018]

Nivolumab (Opdivo) significantly improves overall survival and response rates in previously-treated patients with advanced nonsquamous non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CheckMate 057 trial.

Nivolumab has a manageable adverse event profile and is better tolerated than docetaxel, making it a valuable treatment option for patients who have progressed after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. Keating, GM.[2018]

Nivolumab and pembrolizumab, both PD-1 inhibitors, show a lower risk of severe treatment-related adverse effects (AEs) compared to standard care, with a relative risk of 0.39 for grade 3/4 AEs based on a meta-analysis of 9 trials involving 5,353 patients.

While these therapies are generally well tolerated, they are associated with a significantly increased risk of thyroid dysfunction (hyperthyroidism and hypothyroidism) and skin conditions like pruritus and vitiligo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. Costa, R., Carneiro, BA., Agulnik, M., et al.[2022]

In a study of patients with non-small cell lung cancer treated with nivolumab, those who experienced serious adverse events (grade ≥3) had significantly better overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) compared to those without such events.

The findings suggest that while serious adverse events are typically concerning, they may be associated with a more favorable treatment response in patients receiving nivolumab, indicating a complex relationship between adverse effects and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious Immune-related Adverse Events Are Associated With Greater Efficacy of Nivolumab Therapy Against Non-small Cell Lung Cancer. Blazek, J., Hosek, P., Hrabcova, K., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. [2023]

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

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. [2018]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. [2022]

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

An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers. [2018]

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

Neoadjuvant Nivolumab Checks Lung Cancer. [2019]

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

Nivolumab and immune-mediated colitis. [2023]

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

FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma. [2018]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. [2018]

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

Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. [2022]

10. Greece pubmed.ncbi.nlm.nih.gov

Serious Immune-related Adverse Events Are Associated With Greater Efficacy of Nivolumab Therapy Against Non-small Cell Lung Cancer. [2023]