Nivolumab + deb-TACE for Liver Cancer

Not currently recruiting at 9 trial locations

Overseen By James Harding, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Antivirals

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: HIV/AIDS, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 28

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the effects of combining nivolumab, a drug that helps the immune system fight cancer, with deb-TACE (Drug Eluting Bead Transarterial Chemoembolization), which delivers chemotherapy directly to liver tumors. The focus is on treating liver cancer that cannot be surgically removed or treated with a transplant. Participants will receive nivolumab and undergo the deb-TACE procedure to assess the safety and effectiveness of this combination. Individuals with liver cancer confirmed through scans or tests, who have not been able to undergo surgery, might be suitable for this study. As an Early Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants a chance to contribute to groundbreaking cancer treatment development.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop taking your current medications. However, if you are on corticosteroids or other immunosuppressive medications, you must stop them 14 days before starting the study drug, unless they are inhaled or topical steroids, or low-dose adrenal replacement.

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

Research shows that combining nivolumab with Drug Eluting Bead Transarterial Chemoembolization (deb-TACE) is generally safe for people with liver cancer. Earlier studies not only confirmed the safety of this combination but also showed promising results in fighting tumors, indicating a positive safety profile for this treatment method.

Nivolumab helps the immune system attack cancer, while deb-TACE delivers chemotherapy directly to the liver tumor. Both treatments are well-tolerated individually, and their combination has not raised any unexpected safety issues.

For those considering participation in a clinical trial with these treatments, current research provides reassurance about their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Nivolumab combined with deb-TACE for liver cancer because it offers a unique approach compared to standard treatments like surgery, chemotherapy, or radiofrequency ablation. Unlike traditional methods that primarily target cancer cells directly, Nivolumab is an immunotherapy that helps the immune system recognize and attack cancer cells more effectively. When paired with deb-TACE, which delivers chemotherapy directly to the liver tumor while blocking its blood supply, this combination could enhance the overall effectiveness and safety of treatment. This innovative strategy not only targets the tumor directly but also boosts the body's natural defenses, potentially leading to better outcomes for patients with liver cancer.

What evidence suggests that this trial's treatments could be effective for liver cancer?

Research has shown that combining nivolumab with deb-TACE may offer promise in treating liver cancer. In this trial, participants will join different cohorts to receive the combination treatment. Studies have found that deb-TACE alone effectively manages liver cancer that cannot be surgically removed by delivering chemotherapy directly to the tumor. Adding nivolumab, an immunotherapy that aids the immune system in fighting cancer, might enhance this effect. Early results suggest that this combination is safe and can help shrink or control tumors. This approach could provide new hope for patients with liver cancer. ^{1 2 4 5 6}

Who Is on the Research Team?

James Harding, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with confirmed liver cancer (HCC) that can't be removed by surgery or treated with a transplant. They should have measurable disease, be in good physical condition (ECOG 0 or 1), and have well-functioning bone marrow, liver, and kidneys. People with prior liver transplants, certain other cancers, severe allergies to contrast agents used in scans, HIV/AIDS, active autoimmune diseases (with some exceptions), or on high-dose steroids are excluded.

Inclusion Criteria

My liver, kidneys, and bone marrow are functioning well.

Albumin ≥ 2.8 g/dL

My liver cancer cannot be cured with surgery, but it can be treated with a specific procedure.

Exclusion Criteria

You have had a serious allergic reaction to contrast dye in the past, even with medication to prevent it.

Women of childbearing potential (WOCBP) or sexually active men must use appropriate method(s) of contraception.

I cannot undergo angiography/embolization due to medical reasons.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment

Participants receive nivolumab every two weeks starting 4 weeks prior to deb-TACE

4 weeks

2 visits (in-person)

Treatment

Participants undergo deb-TACE and continue nivolumab every two weeks for up to one year

52 weeks

26 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Drug Eluting Bead Transarterial Chemoembolization
• Nivolumab

Trial Overview The trial is testing the combination of nivolumab (an immunotherapy drug) with deb-TACE—a procedure where chemotherapy drugs are delivered directly to the liver tumor through blood vessels—to see if it's safe and works for treating liver cancer.

How Is the Trial Designed?

Group I: Cohort 3, deb-TACE + Nivolumab Experimental Treatment 2 Interventions

3 eligible participants will undergo deb-TACE on Day 0 (+/- 5 days). Nivolumab will be dosed every two weeks starting 4 weeks prior to deb-TACE (Week 4) and continue every 2 weeks for up to one year. If no participants experience a DLT in the initial group of 3 participants, an additional 3 participants will be added to confirm safety. If less than or equal to 1 of 6 participants experiences a DLT, this will be considered the optimal schedule.

Group II: Cohort 2, deb-TACE + Nivolumab Experimental Treatment 2 Interventions

3 eligible participants will undergo deb-TACE on Day 0 (+/- 5 days). Participants will receive nivolumab every two weeks for up to one year, starting 4 weeks prior to deb-TACE (week -4). Participants in this cohort will not receive nivolumab on the day of deb-TACE. If no participants experience a DLT in the initial group of 3 participants or if 1 of 6 participants experiences a DLT, a new group of participants will be enrolled into Cohort 3.

Group III: Cohort 1, deb-TACE + Nivolumab Experimental Treatment 2 Interventions

3 eligible participants will undergo deb-TACE on Day 0 (+/- 5 days). Two weeks after deb-TACE, participants will begin nivolumab every two weeks for up to one year. If no participants experience a dose limiting toxicity (DLT), or 1 of 6 participants experiences a DLT, a new group of participants will be enrolled into Cohort 2.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Bristol-Myers Squibb

Industry 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

Published Research Related to This Trial

In a study of 1480 cancer patients treated with immune checkpoint inhibitors (ICIs), over 50% experienced hepatic adverse events (AEs), with 14.9% classified as severe (grade 3-4).

The presence of hepatic AEs was linked to poorer overall survival rates, with median survival dropping from 9.0 months for patients without AEs to just 3.3 months for those with severe hepatic AEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pattern and impact of hepatic adverse events encountered during immune checkpoint inhibitors - A territory-wide cohort study. Chan, SL., Yip, TC., Wong, VW., et al.[2021]

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 has a manageable safety profile in patients with advanced hepatocellular carcinoma (HCC), with 68% of select treatment-related adverse events (sTRAEs) resolving after treatment, indicating it can be a viable option for this patient group.

The most common sTRAEs were skin-related (35.5%), with gastrointestinal and hepatic events occurring in about 14% of patients, mostly at grade 1/2 severity, suggesting that early management and patient education on monitoring for these events are crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in Advanced Hepatocellular Carcinoma: Safety Profile and Select Treatment-Related Adverse Events From the CheckMate 040 Study. Julien, K., Leung, HT., Fuertes, C., et al.[2022]

In a meta-analysis of 18 studies involving 5,649 patients with non-small cell lung cancer, first-line therapy using PD-1/PD-L1 inhibitors showed a significantly higher risk of treatment-related adverse events (trAEs) and immune-related adverse events (irAEs) compared to subsequent therapies, indicating a need for careful monitoring in initial treatments.

Despite the higher incidence of adverse events in first-line therapy, the types of trAEs and irAEs were largely similar across different therapy lines, suggesting that while the severity may differ, the overall spectrum of side effects remains consistent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of first and subsequent lines of PD-1/PD-L1 inhibitors monotherapy in non-small cell lung cancer patients: a meta-analysis. Yang, Y., Pang, P., Xie, Z., et al.[2022]

A meta-analysis of nine randomized controlled trials showed that PD-1 inhibitors significantly increase the risk of developing all-grade hepatic adverse events (AEs) in cancer patients, although high-grade AEs were not significantly affected compared to chemotherapy or everolimus.

The combination of nivolumab and ipilimumab resulted in a notably higher risk of all-grade and high-grade hepatic AEs compared to ipilimumab alone, indicating that while PD-1 inhibitors can be effective, they also carry a risk of liver-related side effects, primarily of lower severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and risk of hepatic toxicities with PD-1 inhibitors in cancer patients: a meta-analysis. Zhang, X., Ran, Y., Wang, K., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10244613/

Safety and Efficacy of Drug-Eluting Bead Transarterial ... Drug-eluting bead transarterial chemoembolization (DEB-TACE) has good efficacy in the treatment of unresectable hepatocellular carcinoma ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2468294225001546

A comparative study of DEB-TACE alone and ... The aim of the present study was to compare the efficacy and safety of drug‑eluting beads transarterial chemoembolization (DEB-TACE) with ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.4_suppl.437

Nivolumab (NIVO) and drug eluting bead transarterial ... Conclusions: Nivolumab administered with deb-TACE is safe with antitumor activity. This study provides a needed benchmark for the safety of ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT282901

Nivolumab (NIVO) and drug eluting bead transarterial ... A multicenter pilot study of nivolumab (NIVO) with drug eluting bead transarterial chemoembolization (deb-TACE) in patients (pts) with liver limited ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03143270

NCT03143270 | A Study to Test the Safety and Feasibility ... The purpose of the study is to find out the effects of using nivolumab with Drug Eluting Bead Transarterial Chemoembolization (deb-TACE) in the treatment of ...

6. asco.org asco.org/abstracts-presentations/ABSTRACT352731

Nivolumab (NIVO) and drug eluting bead transarterial ... ... liver limited hepatocellular carcinoma (HCC). Nivolumab (NIVO) and drug ... Conclusions: Nivolumab administered with deb-TACE is safe with antitumor activity.