RYZ811 + RYZ801 for Liver Cancer

(GPC3 Trial)

Overseen By RayzeBio Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: RayzeBio, Inc.

Disqualifiers: Liver transplant, CNS metastasis, others

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

Compensation: Varies

Number of Visits: 144

Duration: 42 days for Cycle 1, 28 days for subsequent cycles

70 Participants Needed

Trial Summary

What is the purpose of this trial?

A single arm, open-label Phase 1/1b study of the theranostic pair RYZ811 (diagnostic) and RYZ801 (therapeutic) to identify and treat subjects with GPC3+ unresectable HCC

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. However, it allows antiviral treatment for HBV or HCV infections, so you might be able to continue some medications. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment RYZ811 + RYZ801 for liver cancer?

Research shows that targeting glypican-3 (GPC3), a protein found in liver cancer cells, with a peptide vaccine can trigger an immune response that helps control the disease. In clinical trials, this approach improved outcomes for patients with liver cancer, suggesting potential effectiveness for treatments like RYZ811 + RYZ801 that also target GPC3. ^{1 2 3 4 5}

Is the treatment RYZ811 + RYZ801 generally safe for humans?

The safety of treatments targeting glypican-3 (GPC3), like the GPC3-peptide vaccine, has been evaluated in clinical trials for various cancers, including liver cancer. These studies found that the GPC3-peptide vaccine was generally well tolerated, with no severe side effects reported, suggesting that similar treatments may also be safe. ^{1 2 4 6 7}

What makes the drug RYZ801 unique for liver cancer treatment?

RYZ801 targets glypican-3 (GPC3), a protein found in high levels on liver cancer cells, making it a promising option for treating this type of cancer. This approach is different because it focuses on a specific marker associated with the cancer, potentially leading to more targeted and effective treatment. ^{1 3 4 5 6}

Research Team

Ye Yuan, MD

Principal Investigator

RayzeBio, Inc.

Eligibility Criteria

This trial is for individuals with a type of liver cancer called Hepatocellular Carcinoma (HCC) that cannot be removed by surgery. Participants must have tumors that test positive for a protein called GPC3. Specific eligibility details are not provided, but typically include factors like overall health status and prior treatments.

Inclusion Criteria

I have recovered from previous treatment side effects, or they are minor and stable.

My liver function is good.

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

Exclusion Criteria

My cancer has spread to the main vein of my liver.

I have a specific type of liver cancer.

I have had a liver transplant or am waiting for one.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Diagnostic

Participants receive RYZ811 to assess safety and tolerability

Up to 1 week

Pre-injection and post-injection visits (up to 144 hours post RYZ811 injection)

Treatment

Participants receive RYZ801 to assess safety and tolerability

42 days for Cycle 1, 28 days for subsequent cycles

Before and after each treatment cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• RYZ801
• RYZ811

Trial Overview The study is testing RYZ811, which helps identify cancer cells, alongside RYZ801 as the treatment. It's an early-phase trial where everyone gets both the diagnostic agent and the therapeutic drug to see if they work well together in targeting HCC.

Participant Groups

Group I: Dose Escalation, Dose Expansion Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

RayzeBio, Inc.

Lead Sponsor

Trials

6

Recruited

540+

Findings from Research

Glypican-3 (GPC3) has been identified as a promising target for immunotherapy in hepatocellular carcinoma (HCC), with a phase I trial showing that a peptide vaccine can induce GPC3-reactive T cells without causing autoimmunity.

In a phase II trial, the GPC3 peptide vaccine significantly reduced the 1-year recurrence rate in patients with GPC3-positive tumors, suggesting its potential as an effective adjuvant therapy for HCC and possibly other GPC3-positive cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer peptide vaccine targeted glypican-3 antigen. Nakatsura, T.[2019]

The GPC3-peptide vaccination was well tolerated in 18 pediatric patients with solid tumors, showing a disease-control rate of 66.7% after 2 months, indicating its potential efficacy as an immunotherapy.

Patients with higher frequencies of GPC3-specific cytotoxic T lymphocytes (CTLs) experienced significantly longer progression-free survival (PFS) and overall survival (OS), suggesting that the vaccine may enhance immune responses against tumors, particularly in cases of hepatoblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of glypican-3-derived peptide vaccine therapy for patients with refractory pediatric solid tumors. Tsuchiya, N., Hosono, A., Yoshikawa, T., et al.[2021]

The GPC3 peptide vaccination was well-tolerated in 33 patients with advanced hepatocellular carcinoma (HCC), showing promising safety and some antitumor efficacy, with one patient achieving a partial response and 19 maintaining stable disease after two months.

The study found that higher frequencies of GPC3-specific cytotoxic T lymphocytes (CTLs) after vaccination correlated with significantly longer overall survival, suggesting that CTL frequency could serve as a predictive marker for treatment outcomes in HCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of a glypican-3-derived peptide vaccine for advanced hepatocellular carcinoma: immunologic evidence and potential for improving overall survival. Sawada, Y., Yoshikawa, T., Nobuoka, D., et al.[2021]

A Phase I clinical trial demonstrated that a peptide derived from glypican-3 (GPC3) shows a strong correlation between immunological responses and clinical outcomes in patients with advanced hepatocellular carcinoma.

The findings suggest that the GPC3-derived peptide vaccine may be a promising therapeutic approach for enhancing immune responses in liver cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A glypican-3-derived peptide vaccine against hepatocellular carcinoma. Sawada, Y., Sakai, M., Yoshikawa, T., et al.[2021]

Glypican-3 (GPC3) is identified as a specific oncofetal antigen overexpressed in hepatocellular carcinoma (HCC) and melanoma, making it a promising tumor marker and target for immunotherapy.

The study demonstrated that GPC3-derived peptides can effectively induce cytotoxic T lymphocytes (CTLs) in HLA-A24(+) and HLA-A2(+) patients, leading to reduced tumor growth in mouse models, and a phase I clinical trial for GPC3 peptide vaccine-based immunotherapy in advanced HCC patients has been initiated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Usefulness of a novel oncofetal antigen, glypican-3, for diagnosis and immunotherapy of hepatocellular carcinoma]. Nishimura, Y., Nakatsura, T., Senju, S.[2019]

The CT017 CAR T cell therapy, targeting the GPC3 antigen in patients with advanced hepatocellular carcinoma (HCC), demonstrated a manageable safety profile, with all patients experiencing cytokine release syndrome (CRS) that resolved after treatment, but no cases of neurotoxicity were observed.

Among the six heavily pretreated patients, there was a 16.7% objective response rate and a 50% disease control rate, indicating promising antitumor activity, with a median overall survival of 7.9 months, suggesting potential efficacy that warrants further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RUNX-3-expressing CAR T cells targeting glypican-3 in patients with heavily pretreated advanced hepatocellular carcinoma: a phase I trial. Fu, Q., Zheng, Y., Fang, W., et al.[2023]

The GPC3 peptide vaccine induced specific immune responses in 11 patients with advanced hepatocellular carcinoma (HCC), leading to the activation of cytotoxic T lymphocytes (CTLs) that infiltrated tumors, suggesting a potential mechanism of action for the vaccine.

The frequency of GPC3-specific CTLs after vaccination was correlated with overall survival, indicating that the vaccine may not only stimulate an immune response but also have implications for patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunological efficacy of glypican-3 peptide vaccine in patients with advanced hepatocellular carcinoma. Tsuchiya, N., Yoshikawa, T., Fujinami, N., et al.[2021]

References

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

Cancer peptide vaccine targeted glypican-3 antigen. [2019]

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

Phase I study of glypican-3-derived peptide vaccine therapy for patients with refractory pediatric solid tumors. [2021]

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

Phase I trial of a glypican-3-derived peptide vaccine for advanced hepatocellular carcinoma: immunologic evidence and potential for improving overall survival. [2021]

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

A glypican-3-derived peptide vaccine against hepatocellular carcinoma. [2021]

5. Japan pubmed.ncbi.nlm.nih.gov

[Usefulness of a novel oncofetal antigen, glypican-3, for diagnosis and immunotherapy of hepatocellular carcinoma]. [2019]

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

RUNX-3-expressing CAR T cells targeting glypican-3 in patients with heavily pretreated advanced hepatocellular carcinoma: a phase I trial. [2023]

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

Immunological efficacy of glypican-3 peptide vaccine in patients with advanced hepatocellular carcinoma. [2021]