Cancer Vaccine + Nivolumab + Ipilimumab for Liver Cancer

Overseen By Colleen Apostol, RN

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Checkpoint inhibitors, Monoclonal antibodies

Disqualifiers: Autoimmune disease, Immunodeficiency, Brain metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 10 weeks

56 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of the trial is the safety and tolerability of administering a vaccine targeting the DNAJB1-PRKACA fusion kinase, in combination with nivolumab and ipilimumab in patients with unresectable or metastatic FLC and with non-FLC solid tumors and to assess the T-cell response.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but it does mention that you should not have had chemotherapy, biological cancer therapy, or radiation within 14 days before the first dose of the study drug. It's best to discuss your current medications with the trial team to get specific guidance.

What data supports the effectiveness of the treatment DNAJB1-PRKACA Fusion Kinase Peptide Vaccine, FLC-Vac, DNAJB1-PRKACA Fusion Kinase Peptide Vaccine, Ipilimumab, Yervoy, Nivolumab, Opdivo for liver cancer?

Research on a similar vaccine targeting the DNAJB1-PRKACA fusion protein in fibrolamellar hepatocellular carcinoma showed that it induced strong immune responses and led to a patient experiencing over 21 months of relapse-free survival, suggesting potential effectiveness in targeting this specific cancer type. ^{1 2 3 4 5}

Is the combination of cancer vaccine, Nivolumab, and Ipilimumab generally safe for humans?

The safety of peptide-based cancer vaccines has been evaluated in various studies, showing that they are generally well-tolerated with no severe adverse events reported. However, specific safety data for the combination of the cancer vaccine with Nivolumab and Ipilimumab for liver cancer is not available in the provided research. ^{1 2 3 5 6}

What makes the Cancer Vaccine + Nivolumab + Ipilimumab treatment unique for liver cancer?

This treatment is unique because it combines a cancer vaccine targeting a specific fusion protein (DNAJB1-PRKACA) with two immunotherapy drugs, Nivolumab and Ipilimumab, which help the immune system attack cancer cells. This combination approach is novel for liver cancer, as there are limited standard treatments available for this condition. ^{1 2 5 7 8}

Research Team

Mark Yarchoan, MD

Principal Investigator

Johns Hopkins Medical Institution

Eligibility Criteria

This trial is for individuals with a rare liver cancer called fibrolamellar hepatocellular carcinoma (FLC) that can't be removed by surgery or has spread. Participants must be over 12 years old, weigh at least 40 kg if under 18, and have a tumor that can be biopsied. They need to have good organ function and performance status, not be on certain medications or treatments recently, and agree to use birth control.

Inclusion Criteria

Ability to understand and willingness to sign a written informed consent document.

My cancer has a specific genetic change known as DNAJB1-PRKACA fusion.

My cancer is advanced, cannot be surgically removed, and tests positive for a specific genetic change.

Exclusion Criteria

I haven't taken high-dose steroids or other immune-weakening drugs in the last week.

Have received other approved or investigational agents or device within 28 days of the first dose of study drug.

The doctor will decide if there are any other medical, mental health, or social reasons that make it unsuitable for you to participate in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the DNAJB1-PRKACA peptide vaccine in combination with nivolumab and ipilimumab

10 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Treatment Details

Interventions

• DNAJB1-PRKACA Fusion Kinase Peptide Vaccine
• Ipilimumab
• Nivolumab

Trial Overview The trial tests the safety of a new vaccine targeting DNAJB1-PRKACA fusion kinase in combination with two immunotherapy drugs: Nivolumab and Ipilimumab. It aims to see how well patients' T-cells respond to this treatment regimen for advanced FLC.

Participant Groups

Group I: DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

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

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Fibrolamellar Cancer Foundation

Collaborator

Trials

3

Recruited

80+

Fibrolamellar Cancer Foundation

Collaborator

Trials

4

Recruited

110+

Findings from Research

A clinical trial using vaccines targeting specific cancer peptides (RNF43 and TOMM34) in combination with tegafur-uracil/Leucovorin (UFT/LV) for advanced colorectal cancer showed good tolerance and no adverse events.

Patients who developed cytolytic T-lymphocyte (CTL) responses to both RNF43 and TOMM34 had the highest long-term survival rates, indicating the potential effectiveness of these targeted vaccines in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical study of Peptide-cocktail vaccination with tegafur-uracil/leucovorin for advanced colorectal cancer]. Sugiura, F., Inoue, K., Okuno, K., et al.[2020]

The phase I clinical trial involving 18 patients with advanced colorectal cancer demonstrated that a combination vaccine using multiple peptides was well tolerated, with no severe systemic adverse events reported.

The treatment induced a dose-dependent immune response, with patients showing better outcomes (median overall survival of 27.8 months) when specific cytotoxic T lymphocytes were activated, highlighting the potential efficacy of this peptide-based vaccine approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of combination vaccine treatment of five therapeutic epitope-peptides for metastatic colorectal cancer; safety, immunological response, and clinical outcome. Hazama, S., Nakamura, Y., Takenouchi, H., et al.[2021]

The multi-target vaccine composed of peptides from cancer-testis antigens and VEGFRs was well-tolerated in a Phase I trial with 9 patients suffering from advanced pancreatic cancer, showing no severe adverse events.

Four out of nine patients experienced clinical benefits, with median progression-free survival of 90 days and overall survival of 207 days, indicating potential efficacy of the vaccine in this difficult-to-treat population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunological responses to a multi-peptide vaccine targeting cancer-testis antigens and VEGFRs in advanced pancreatic cancer patients. Okuyama, R., Aruga, A., Hatori, T., et al.[2021]

The DNAJB1-PRKACA fusion transcript is identified as the main driver of fibrolamellar hepatocellular carcinoma, and specific neoantigens derived from this fusion can effectively stimulate CD8+ and CD4+ T cell responses, indicating a potential target for immunotherapy.

In a case study of a patient with recurrent disease, vaccination with DNAJB1-PRKACA-derived peptides led to a strong and lasting T cell response, resulting in over 21 months of relapse-free survival, showcasing the efficacy of this targeted immunotherapy approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The oncogenic fusion protein DNAJB1-PRKACA can be specifically targeted by peptide-based immunotherapy in fibrolamellar hepatocellular carcinoma. Bauer, J., Köhler, N., Maringer, Y., et al.[2022]

The four-peptide vaccination for advanced biliary tract cancer was well tolerated by patients, with no severe adverse events (grade 3 or 4) reported, indicating a favorable safety profile.

Among the nine patients treated, six showed clinical responses and seven exhibited peptide-specific T-cell immune responses, with median progression-free survival and overall survival of 156 and 380 days, respectively, suggesting potential efficacy of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Vaccination with Multiple Peptides Derived from Cancer-Testis Antigens Can Maintain a Specific T-cell Response and Achieve Disease Stability in Advanced Biliary Tract Cancer. Aruga, A., Takeshita, N., Kotera, Y., et al.[2020]

The VEGFR-targeted peptide vaccines were safe for patients with unresectable hepatocellular carcinoma (HCC), with no severe adverse events reported during the study involving 22 patients.

The vaccines successfully induced specific immune responses in a majority of patients, leading to improved progression-free survival (PFS) in those with strong immune responses, although overall survival rates did not show statistically significant differences compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase I / II study of vascular endothelial growth factor receptor peptide vaccines for patients with hepatocellular carcinoma. Yoshimaru, Y., Nagaoka, K., Tanaka, K., et al.[2023]

A clinical trial using cancer-specific peptide vaccines derived from RNF43 and TOMM34, combined with UFT and Leucovorin, was well tolerated in patients with advanced colorectal cancer, showing no serious adverse events.

Patients who developed cytotoxic T lymphocyte (CTL) responses against the peptides had long-term survival, indicating the potential efficacy of these vaccines in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment outcome of peptide vaccination for advanced colorectal cancer]. Sugiura, F., Inoue, K., Kogita, A., et al.[2020]

In a phase I trial involving 16 patients with pancreatic ductal adenocarcinoma (PDAC), the individualized neoantigen vaccine autogene cevumeran was found to be tolerable and successfully induced high levels of neoantigen-specific T cells in half of the patients, suggesting a promising immune response.

Patients who developed vaccine-expanded T cells had significantly longer recurrence-free survival (not reached) compared to those who did not, indicating that the vaccine may help delay the recurrence of PDAC when combined with atezolizumab and chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Rojas, LA., Sethna, Z., Soares, KC., et al.[2023]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Clinical study of Peptide-cocktail vaccination with tegafur-uracil/leucovorin for advanced colorectal cancer]. [2020]

2. England pubmed.ncbi.nlm.nih.gov

A phase I study of combination vaccine treatment of five therapeutic epitope-peptides for metastatic colorectal cancer; safety, immunological response, and clinical outcome. [2021]

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

Immunological responses to a multi-peptide vaccine targeting cancer-testis antigens and VEGFRs in advanced pancreatic cancer patients. [2021]

4. England pubmed.ncbi.nlm.nih.gov

The oncogenic fusion protein DNAJB1-PRKACA can be specifically targeted by peptide-based immunotherapy in fibrolamellar hepatocellular carcinoma. [2022]

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

Long-term Vaccination with Multiple Peptides Derived from Cancer-Testis Antigens Can Maintain a Specific T-cell Response and Achieve Disease Stability in Advanced Biliary Tract Cancer. [2020]

6. Netherlands pubmed.ncbi.nlm.nih.gov

A randomized phase I / II study of vascular endothelial growth factor receptor peptide vaccines for patients with hepatocellular carcinoma. [2023]

7. Japan pubmed.ncbi.nlm.nih.gov

[Treatment outcome of peptide vaccination for advanced colorectal cancer]. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. [2023]