Nivolumab for Cancer

Recruiting at 54 trial locations

Overseen By Brian S. Henick

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anticancer investigational agents

Disqualifiers: Chemotherapy, Radiotherapy, Allogeneic transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 4

Duration: Up to 2 years

300 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase Ib trial studies the side effects of nivolumab and to see how well it works in treating patients with autoimmune disorders and cancer that has spread to other places in the body or cannot removed by surgery. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

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 have received certain types of immunotherapy, there are specific waiting periods before starting nivolumab. It's best to discuss your current medications with the trial team to get a clear answer.

What data supports the effectiveness of the drug Nivolumab for cancer?

Nivolumab has shown significant effectiveness in treating advanced non-small cell lung cancer (NSCLC), with studies indicating better overall survival and response rates compared to traditional chemotherapy. It is also approved for use in several other cancers, including melanoma and renal cell cancer, highlighting its broad antitumor activity. ^{1 2 3 4 5}

Is Nivolumab safe for humans?

Nivolumab, also known as Opdivo, is generally considered safe, but it can cause immune-related side effects, which are usually manageable but can be severe in some cases. These side effects may include inflammation of the colon (colitis) and blood-related issues, which are rare but potentially serious. Combining Nivolumab with other drugs like Ipilimumab may increase the risk of these side effects. ^{6 7 8 9 10}

How is the drug Nivolumab unique in treating cancer?

Nivolumab is unique because it is a PD-1 immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells, offering a new option for patients who have already undergone other treatments. It is administered intravenously and has shown better survival rates and tolerability compared to traditional chemotherapy drugs like docetaxel in certain cancers. ^{3 4 5 11 12}

Research Team

Hussein A. Tawbi

Principal Investigator

University of Texas MD Anderson Cancer Center LAO

Eligibility Criteria

Adults with advanced or inoperable cancer and an autoimmune disorder (like lupus, rheumatoid arthritis, or multiple sclerosis) can join this trial. They should have a life expectancy over 12 weeks, be relatively active (ECOG 0-2), and have not had certain treatments recently. Those with controlled hepatitis B/C are eligible; however, pregnant women must use contraception.

Inclusion Criteria

My kidney function, measured by creatinine level or GFR, is within the normal range.

Your total bilirubin level is not more than twice the normal limit at the study hospital.

I am HIV-positive, on treatment, and my viral load has been undetectable for the last 6 months.

Exclusion Criteria

I haven't had chemotherapy or radiotherapy in the last 2 weeks.

You are currently taking any other experimental cancer drugs.

I have been treated with drugs targeting PD-1 or PD-L1 before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive nivolumab intravenously over 30 minutes every 4 weeks for up to 2 years, with regular collection of blood, CSF, tissue, stool, and urine samples

Up to 2 years

Every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

100 days

Treatment Details

Interventions

• Nivolumab

Trial Overview The trial is testing Nivolumab's effectiveness and safety for patients who have both cancer and autoimmune diseases. It's a phase Ib study to see how well the immune system responds to this monoclonal antibody treatment in attacking cancer cells that spread or cannot be surgically removed.

Participant Groups

Group I: Treatment (nivolumab) Experimental Treatment 2 Interventions

Patients receive nivolumab IV over 30 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood, CSF, tissue, stool, and urine samples throughout the trial.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Nivolumab, a PD-1 receptor inhibitor, shows an objective response rate of 18% and a 1-year overall survival rate of 45% in patients with advanced non-small-cell lung cancer, based on a meta-analysis of 20 studies involving 3404 patients.

The presence of PD-L1 expression in patients is associated with a better response to nivolumab, indicating that PD-L1 status can help predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The benefit and risk of nivolumab in non-small-cell lung cancer: a single-arm meta-analysis of noncomparative clinical studies and randomized controlled trials. Zhao, B., Zhang, W., Yu, D., et al.[2019]

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

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 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 (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]

Combining nivolumab and ipilimumab shows improved effectiveness in treating metastatic melanoma compared to using either drug alone, based on a retrospective analysis of approximately 7700 patients.

The combination therapy presents a safety profile that includes immune-related adverse events from both drugs, indicating that while the combination is effective, it also carries a heightened risk of toxicity that needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. Soldatos, TG., Dimitrakopoulou-Strauss, A., Larribere, L., et al.[2022]

In a study of 45 patients with metastatic melanoma treated with the combination of nivolumab and ipilimumab, the disease control rate was 54% and the objective response rate was 29%, indicating moderate efficacy in a real-world setting.

The treatment had a high toxicity profile, with 88% of patients experiencing adverse events, and 44% discontinuing treatment due to these events, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world efficacy and toxicity of combined nivolumab and ipilimumab in patients with metastatic melanoma. Parakh, S., Randhawa, M., Nguyen, B., et al.[2019]

In a study of 79 pre-treated patients with advanced non-small cell lung cancer, nivolumab significantly prolonged progression-free survival, especially in patients who had a partial response to prior treatments.

The occurrence of skin rash during nivolumab treatment was associated with improved long-term survival, suggesting that this side effect may indicate a favorable response to the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Pleiotropic Effects of Nivolumab in Pretreated Advanced or Recurrent Non-small Cell Lung Cancer Cases. Akano, Y., Kuribayashi, K., Funaguchi, N., et al.[2020]

Nivolumab, an immune checkpoint inhibitor for metastatic melanoma, can cause immune-related adverse events (irAEs) such as colitis, which were observed in two patients after treatment.

The development of these irAEs is linked to a Th1 dominant immune response, and serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6) may serve as potential biomarkers to monitor and manage these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe colitis after PD-1 blockade with nivolumab in advanced melanoma patients: potential role of Th1-dominant immune response in immune-related adverse events: two case reports. Yoshino, K., Nakayama, T., Ito, A., et al.[2020]

In a meta-analysis of five studies involving 2399 patients, nivolumab was found to significantly lower the risk of hematological toxicities such as anemia, neutropenia, and leukopenia compared to other treatments.

The relative risks for these conditions were notably low, indicating that nivolumab may be a safer option regarding hematological side effects, which is important for clinicians when considering treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. Shi, Z., Liu, X., Chen, M., 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, a monoclonal antibody targeting the programmed death receptor-1, has shown promising efficacy in treating advanced malignant melanoma, with nearly 25% of patients achieving a partial tumor response in a phase II trial involving previously treated stage III/IV patients.

The treatment demonstrated a durable clinical benefit, with a median progression-free survival of 172 days and an acceptable safety profile, as less than 18% of patients experienced severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review of its use in patients with malignant melanoma. Deeks, ED.[2021]

References

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

The benefit and risk of nivolumab in non-small-cell lung cancer: a single-arm meta-analysis of noncomparative clinical studies and randomized controlled trials. [2019]

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

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. [2022]

3. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. [2022]

7. Australia pubmed.ncbi.nlm.nih.gov

Real-world efficacy and toxicity of combined nivolumab and ipilimumab in patients with metastatic melanoma. [2019]

8. Greece pubmed.ncbi.nlm.nih.gov

Analysis of Pleiotropic Effects of Nivolumab in Pretreated Advanced or Recurrent Non-small Cell Lung Cancer Cases. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Severe colitis after PD-1 blockade with nivolumab in advanced melanoma patients: potential role of Th1-dominant immune response in immune-related adverse events: two case reports. [2020]

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

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. [2023]

11. England pubmed.ncbi.nlm.nih.gov

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

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

Nivolumab: a review of its use in patients with malignant melanoma. [2021]