Nivolumab for Liver Cancer

(CheckMate 9DX Trial)

Not currently recruiting at 422 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether nivolumab, an immunotherapy drug, can prevent liver cancer from returning after treatment. Researchers compare nivolumab to a placebo to determine if it prolongs cancer-free periods. Individuals who recently underwent surgery or treatment that removed all visible liver cancer and are at high risk for recurrence can participate. This includes those with liver cancer unrelated to viruses or linked to hepatitis B or C. Participants should not have other types of liver cancer or signs of metastasis. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that nivolumab is generally safe for treating liver cancer, but some risks exist. In earlier studies, a small number of patients experienced serious side effects. About 0.9% of patients faced life-threatening reactions, such as lung inflammation (pneumonitis) or a muscle condition called myasthenia gravis. Although rare, these cases highlight the need for careful monitoring during treatment.

Overall, nivolumab has shown promise in shrinking or eliminating tumors. However, some patients discontinued treatment due to side effects like severe tiredness and skin problems. Notably, the FDA has already approved nivolumab for other types of cancer, suggesting confidence in its general safety.

Prospective trial participants should discuss the risks and benefits with a healthcare provider. This discussion can help weigh the potential side effects against the treatment's benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Nivolumab is unique because it is an immunotherapy drug that harnesses the body's immune system to fight liver cancer. Unlike traditional treatments like chemotherapy or targeted therapies, which directly attack the cancer cells, nivolumab works by blocking a protein called PD-1. This blockade allows immune cells to recognize and destroy cancer cells more effectively. Researchers are excited about nivolumab's potential because it offers a different approach to treating liver cancer, possibly leading to better outcomes and fewer side effects compared to standard treatments.

What evidence suggests that nivolumab might be an effective treatment for liver cancer?

Research has shown that nivolumab, which participants in this trial may receive, effectively treats liver cancer, specifically hepatocellular carcinoma (HCC). In studies, patients who received only nivolumab experienced positive outcomes, with some tumors shrinking or disappearing. Compared to other treatments like lenvatinib or sorafenib, nivolumab has performed better in certain situations. Additionally, real-world data supports its effectiveness in treating HCC that cannot be surgically removed, particularly in regions with high hepatitis B infection rates. This evidence suggests that nivolumab can be a promising option for extending the time patients remain free from cancer recurrence. ^{2 3 6 7 8}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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, 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]

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 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 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, 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]

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]

Citations

1. opdivohcp.com opdivohcp.com/efficacy/hcc

Efficacy Data for Hepatocellular Carcinoma (HCC) Liver-related serious adverse reactions occurred in 17% of patients receiving OPDIVO with YERVOY, including Grade 3-4 events in 16% of patients. The most ...

2. opdivo.com opdivo.com/advanced-hcc/clinical-trial-results/unresectable-immunotherapy-combination

Clinical trial results for previously untreated advanced liver ... More people given OPDIVO + YERVOY had their tumors shrink or completely disappear compared to targeted therapies lenvatinib or sorafenib ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7338665/

Real-World Outcomes of Nivolumab in Patients With ... In conclusion, our study demonstrates that nivolumab monotherapy is clinically efficacious in treating unresectable HCC in an endemic area of HBV infection.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9644453/

Low-dose nivolumab in advanced hepatocellular carcinoma Low-dose nivolumab may be effective with manageable toxicity and can be an alternative option to reduce financial toxicity in patients with advanced HCC.

5. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-ipilimumab-unresectable-or-metastatic-hepatocellular-carcinoma

FDA approves nivolumab with ipilimumab for unresectable ... Median OS was 23.7 months (95% CI: 18.8, 29.4) in the nivolumab + ipilimumab arm and 20.6 months (95% CI: 17.5, 22.5) in the lenvatinib or ...

6. opdivohcp.com opdivohcp.com/safety/hcc/opdivo-yervoy

Safety Profile in Hepatocellular Carcinoma (HCC) - Opdivo Fatal adverse reactions occurring in 3 (0.9%) patients who received OPDIVO as a single agent; these included pneumonitis (n=2) and myasthenia gravis. In ...

7. karger.com karger.com/pjg/article/doi/10.1159/000543288/918492/Five-year-sustained-response-to-nivolumab-in

Five-Year Sustained Response to Nivolumab in ... Second-line nivolumab, although yielding a rapid clinical and biochemical response, was permanently ceased after 12 weeks due to a grade 3 ...

8. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.32206

Nivolumab in patients with advanced hepatocellular ... The median overall survival from the time of nivolumab initiation was 5.9 months (95% CI, 3 months to upper bound not estimable), with a median ...