RYZ811 + RYZ801 for Liver Cancer

(GPC3 Trial)

Recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called RYZ801 for liver cancer that cannot be removed by surgery. The goal is to determine if RYZ801 can benefit individuals with a specific type of liver cancer that shows a marker called GPC3. The trial also includes RYZ811 (Gallium 68-labeled peptide binder) as part of the treatment process. It seeks participants who have previously undergone liver cancer treatments but still have a type that standard procedures cannot treat. Individuals diagnosed with liver cancer, who have tried at least one other treatment, and have good liver and kidney function may be suitable for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

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.

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

Research shows that patients have tolerated RYZ801 well so far. As of mid-2023, no serious side effects have been linked to the treatment, and no patients have stopped taking it due to side effects. This suggests that RYZ801 might be safe for short-term use. However, as this is an early-stage trial, further studies are needed to fully understand its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about RYZ801 for liver cancer because it offers a new mechanism of action compared to standard treatments like sorafenib or lenvatinib, which are tyrosine kinase inhibitors. RYZ801 works by targeting specific pathways involved in liver cancer cell growth, potentially offering a more precise attack on the cancer cells. Additionally, this treatment might have a different side effect profile, which could mean a better quality of life for patients during treatment. These features make RYZ801 a promising new option in the fight against liver cancer.

What evidence suggests that RYZ801 might be an effective treatment for liver cancer?

Research has shown that RYZ801, a treatment under study in this trial, could be promising for liver cancer. It targets a protein called Glypican-3 (GPC3), present in many liver tumors, to deliver a radioactive substance, Ac225, directly to the cancer cells. Early studies demonstrated that this method effectively reaches the liver, suggesting potential benefits. The treatment has been well tolerated, with no serious side effects reported. These initial findings offer hope for its effectiveness in treating liver cancer that cannot be surgically removed. ^{1 2 3 5 6}

Who Is on the Research Team?

Heying Duan, MD

Principal Investigator

RayzeBio, Inc.

Are You a Good Fit for This Trial?

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 had a liver transplant or am waiting for one.

I am allergic to 68Ga, 225Ac, or ingredients in RYZ811 or RYZ801.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

RayzeBio, Inc.

Lead Sponsor

Trials

6

Recruited

540+

Published Research Related to This Trial

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) 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 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]

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]

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 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]

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]

Citations

1. rayzebio.com rayzebio.com/pipeline/hepatocellular-carcinoma/

RYZ801 targeting GPC3 for hepatocellular carcinoma (HCC) RYZ801 is our novel proprietary peptide which targets GPC3 for delivery of Ac225 for the treatment of HCC. Preclinical biodistribution studies in the liver ...

2. peptidream.com peptidream.com/en/pipeline/

Pipeline｜PEPTIDREAM INC ペプチドリーム株式会社 PeptiDream has a robust drug discovery pipeline developed internally and in collaboration with leading pharmaceutical and biotech companies.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06726161

NCT06726161 | Study of the Theranostic Pair RYZ811 ... Study of the Theranostic Pair RYZ811 (Diagnostic) and RYZ801 (Therapeutic) to Identify and Treat Subjects With GPC3+ Unresectable HCC (GPC3). ClinicalTrials.gov ...

4. rayzebio.com rayzebio.com/wp-content/uploads/2023/04/Liver_cancer_summit_2023_Poster_279_FINAL.pdf

GPC3 targeted radiopharmaceutical therapy for HCC Glypican-3 expression is correlated with poor prognosis in hepatocellular carcinoma. Cancer Sci. 2009;100(8):1403–1407. 6. Sun H, Xing C, Jiang S, et al.

5. bms.com bms.com/assets/bms/us/en-us/pdf/investor-info/2023/bmy-ryzb-infographic.pdf

BMY-RYZB Infographic (PDF) As of June 30, 2023, treatment has been well tolerated with no treatment-related serious adverse events or dose discontinuations due to any adverse event.

6. sec.gov sec.gov/Archives/edgar/data/1825367/000119312523220093/d492091ds1.htm

S-1 The five-year survival rate for all liver cancer patients is approximately 20% and the survival rate of patients with advanced stage liver cancer is ...