Nivolumab for Liver Cancer

(CheckMate 9DX Trial)

Recruiting at 355 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Must not be taking: Live vaccines

Disqualifiers: Metastasis, Liver transplant, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

545 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will investigate if nivolumab will improve recurrence-free survival (RFS) compared to placebo in participants with HCC who have undergone complete resection or have achieved a complete response after local ablation, and who are at high risk of recurrence

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that Nivolumab, used for liver cancer, can lead to longer survival and manageable safety in patients with advanced liver cancer. It has also been effective in improving survival in patients with advanced lung cancer, suggesting its potential benefit in treating other cancers. ^{1 2 3 4 5}

Is Nivolumab safe for humans?

Nivolumab, also known as Opdivo, has been associated with some immune-related side effects, including liver injury and hepatitis B reactivation, which can lead to treatment delays or discontinuation. It is important to monitor for these potential side effects during treatment. ^{3 6 7 8 9}

How is the drug Nivolumab unique for treating liver cancer?

Nivolumab is unique because it is an immune checkpoint inhibitor that helps the body's immune system recognize and attack cancer cells, which is different from traditional chemotherapy. It has shown effectiveness in treating advanced liver cancer (hepatocellular carcinoma) and is administered intravenously, typically every two weeks. ^{1 3 4 10 11}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for individuals with Hepatocellular Carcinoma (HCC) who have had surgery or ablation and are at high risk of the cancer coming back. It's open to those with non-viral related HCC, HBV-HCC, or HCV-HCC, a good performance status, and no prior treatments for HCC. People can't join if they've had certain types of liver cancer, evidence of spread, previous cancer therapies including transplant or are on a transplant waiting list.

Inclusion Criteria

I had surgery or ablation for liver cancer as my first treatment.

My liver cancer is not caused by a virus, or it's due to hepatitis B or C.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have had treatments for liver cancer before.

I have not received a live vaccine in the last 30 days.

My cancer has spread or I have more than one type of cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either nivolumab or placebo to assess recurrence-free survival

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Nivolumab
• Placebo

Trial Overview The study is testing whether Nivolumab can prevent cancer from returning in patients who've undergone curative treatment for liver cancer compared to a placebo. Participants will be randomly assigned to receive either Nivolumab or a placebo without knowing which one they're getting.

Participant Groups

Group I: Arm A Experimental Treatment 1 Intervention

Group II: Arm B Placebo Group 1 Intervention

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

In a study of 11 patients with advanced hepatocellular carcinoma (HCC), nivolumab therapy demonstrated a high disease control rate of 81.8% and an objective response rate of 63.6%, indicating its efficacy as a treatment option.

No adverse effects related to nivolumab were reported, suggesting a favorable safety profile, especially for patients who did not respond to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial experience of anti-PD1 therapy with nivolumab in advanced hepatocellular carcinoma. Feng, D., Hui, X., Shi-Chun, L., et al.[2022]

Nivolumab, a PD-1 inhibitor, showed durable responses and increased overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC), with a median OS of 28.1 months for patients with PD-L1 expression ≥1% compared to 16.6 months for those with <1%.

The study found that higher expression of PD-1 and PD-L1, along with specific inflammatory gene signatures, were associated with improved survival and response to treatment, suggesting that the immune response plays a significant role in the effectiveness of nivolumab in HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of inflammatory biomarkers with clinical outcomes in nivolumab-treated patients with advanced hepatocellular carcinoma. Sangro, B., Melero, I., Wadhawan, S., et al.[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]

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]

A retrospective analysis of adverse events related to PD-1/PD-L1 inhibitors revealed a significant association between Pembrolizumab and hepatitis B reactivation (HBVr), with a reporting odds ratio of 2.32, indicating a higher risk compared to other treatments.

No cases of HBVr were reported with Ipilimumab or Avelumab, suggesting that not all immune checkpoint inhibitors carry the same risk, highlighting the need for further prospective studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. Burns, EA., Muhsen, IN., Anand, K., et al.[2023]

Nivolumab, an immune checkpoint inhibitor, shows effectiveness in treating hepatocellular carcinoma (HCC), particularly in a subset of patients receiving it in the neoadjuvant setting, with marked treatment responses observed in some cases.

Long-term nivolumab therapy may lead to specific liver injuries, such as bile duct damage and ductular reactions, indicating the need for further studies to understand these effects and identify patients who may benefit most from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morphology of tumor and nontumor tissue in liver resection specimens for hepatocellular carcinoma following nivolumab therapy. Simoes, CC., Thung, SN., Fiel, MI., et al.[2023]

Nivolumab has been demonstrated to be an effective treatment for hepatocellular carcinoma (HCC), indicating its potential as a therapeutic option for this type of liver cancer.

The treatment is also reported to be safe, suggesting that it can be administered with a manageable side effect profile for patients with HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-Programmed death-1 therapy in advanced hepatocellular carcinoma: A real-world experience. Al Jarroudi, O., Chaabouni, H., Ulusakarya, A., et al.[2021]

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]

References

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

Initial experience of anti-PD1 therapy with nivolumab in advanced hepatocellular carcinoma. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Association of inflammatory biomarkers with clinical outcomes in nivolumab-treated patients with advanced hepatocellular carcinoma. [2022]

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

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

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

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

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

Predictive value of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in advanced hepatocellular carcinoma patients treated with anti-PD-1 therapy. [2021]

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

Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis. [2023]

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

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. [2023]

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

Morphology of tumor and nontumor tissue in liver resection specimens for hepatocellular carcinoma following nivolumab therapy. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Risk of Liver Toxicity with Nivolumab Immunotherapy in Cancer Patients. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Anti-Programmed death-1 therapy in advanced hepatocellular carcinoma: A real-world experience. [2021]

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

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