Nivolumab for Cancer

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Active brain metastases, Autoimmune disease, HIV, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: Up to 2 years

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests nivolumab, an immunotherapy drug designed to help the immune system fight cancer. It targets individuals with solid tumors that have either metastasized or cannot be surgically removed, specifically those with an ARID1A mutation and CXCL13 expression. Participants must have a tumor confirmed through medical imaging and provide tumor tissue for analysis. The study examines whether nivolumab can control the disease by inhibiting tumor cell growth and spread. As a Phase 2 trial, the 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, you cannot be on certain immunosuppressive medications or high doses of corticosteroids (more than 10 mg of prednisone daily) within 14 days of 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. In clinical trials, over 20% of patients reported common side effects such as tiredness, muscle and joint pain, cough, and shortness of breath. These side effects are usually manageable.

Nivolumab, an immunotherapy drug, helps the immune system fight cancer. Its use in other cancer treatments has provided some confidence about its safety. However, serious side effects can occur, though they are less common. It is crucial to discuss the risks and benefits with healthcare providers before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Nivolumab is unique because it harnesses the power of the immune system to fight cancer differently than traditional treatments like chemotherapy or radiation. Most standard treatments work by directly attacking cancer cells, but nivolumab is an immune checkpoint inhibitor. It blocks a protein called PD-1, which cancer cells use to hide from the immune system. By blocking this protein, nivolumab enables the immune system to recognize and destroy cancer cells more effectively. Researchers are excited about nivolumab because it offers a novel way to treat cancer, potentially leading to longer-lasting responses and improved survival rates for patients.

What evidence suggests that nivolumab might be an effective treatment for metastatic or unresectable solid tumors?

Research has shown that nivolumab can effectively treat certain types of cancer. In earlier studies, patients with advanced melanoma who received nivolumab, either alone or with other treatments, lived longer, with some surviving over six years. Another study found that nivolumab worked well on its own for patients with advanced non-small cell lung cancer (NSCLC) who had been previously treated, showing promising results. Overall, these findings suggest that nivolumab may enhance the immune system's ability to identify and attack cancer cells. ^{5 6 7 8 9}

Who Is on the Research Team?

Funda Meric-Bernstam, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with solid tumors that can't be removed by surgery or have spread, which also have ARID1A mutation and CXCL13 expression. They should not have serious medical issues, autoimmune diseases, recent immunosuppressive treatments, active infections like hepatitis B/C or HIV, brain metastases requiring steroids, or a history of certain cancers within the last 3 years.

Inclusion Criteria

My cancer can be measured on scans according to specific criteria.

I am fully active or can carry out light work.

I can provide a sample of my tumor for testing, either from a past surgery or a new biopsy.

Exclusion Criteria

I have previously been treated with specific immune-targeting cancer drugs.

I haven't had active cancer in the last 3 years, except for certain curable types.

Any serious or uncontrolled medical disorder, that in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive nivolumab and relatlimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 2 years

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab

Trial Overview The trial is testing Nivolumab's effectiveness on patients with specific genetic markers in their tumors. It's a phase II study to see if this drug can help the immune system fight cancer and prevent tumor growth.

How Is the Trial Designed?

Group I: Treatment (nivolumab) Experimental Treatment 1 Intervention

Patients receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

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]

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 (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, 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 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, 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 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]

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]

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]

Citations

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Systematic Review on the Effectiveness and Outcomes of ... With a median follow-up time of 19.2 months, the median overall survival (OS) was reported at 21.9 months, and the 12-month PFS rate was 26.3%, ...

2. opdivohcp.com opdivohcp.com/efficacy

Efficacy Information | OPDIVO® (nivolumab) In NSCLC patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, immune-mediated pneumonitis occurred in 9% (50/576) of patients, ...

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Clinical Trial Results Select your cancer type above to see how OPDIVO, alone or in combination with other therapies, performed in clinical trials.

4. news.bms.com news.bms.com/news/details/2021/Six-and-a-Half-Year-Outcomes-for-Opdivo-nivolumab-in-Combination-with-Yervoy-ipilimumab-Continue-to-Demonstrate-Durable-Long-Term-Survival-Benefits-in-Patients-with-Advanced-Melanoma/default.aspx

Six-and-a-Half-Year Outcomes for Opdivo (nivolumab) in ... With a minimum follow-up of 6.5 years, median overall survival (OS) was 72.1 months with Opdivo plus Yervoy (95% CI: 38.2-NR), the longest ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S152573042030231X

Real-World Effectiveness of Nivolumab Monotherapy After ... This study confirmed the effectiveness of nivolumab monotherapy for previously treated advanced NSCLC in real-world clinical practice.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33808781/

Safety and Treatment Outcomes of Nivolumab for the ... Primary outcomes included overall response rate (ORR) of 19.3%, median progression-free survival (PFS) of 3.9 months, 1-year PFS rate of 16.8%, ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK596614/

Nivolumab (Opdivo) - NCBI Bookshelf - NIH Evidence from 1 clinical trial demonstrated that adding Opdivo to chemotherapy before surgery in patients with early-stage NSCLC lowered the chances of cancer ...

8. opdivohcp.com opdivohcp.com/efficacy/nsclc/opdivo

5 years of OS data in 2L mNSCLC 1,2 - Opdivo In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and ...

9. jto.org jto.org/article/S1556-0864(24)02355-4/fulltext

Long-Term Survival Outcomes With First-Line Nivolumab ... Median OS was 35.4 months in this population, and the 5-year OS rate was 37% (Fig. 4A). By the data cutoff dates for CheckMate 227 and CheckMate ...