Study of the Theranostic Pair RYZ811 (Diagnostic) and RYZ801 (Therapeutic) to Identify and Treat Subjects With GPC3+ (Glypican-3) Unresectable HCC (GPC3)

April 6, 2026 updated by: RayzeBio, Inc.

Phase 1/2 Randomized, Controlled, Open-label Trial of Theranostic Pair RYZ811 (Diagnostic) and RYZ801 (Therapeutic) to Identify and Treat Subjects With GPC3+ Unresectable Hepatocellular Carcinoma (HCC)

Phase 1/2 randomized, controlled, open-label trial of theranostic pair RYZ811 (diagnostic) and RYZ801 (therapeutic) to identify and treat subjects with GPC3+ unresectable hepatocellular carcinoma (HCC)

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

590

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Research Facility
      • Tucson, Arizona, United States, 85719
        • Recruiting
        • Research Facility
    • California
      • Orange, California, United States, 92868
        • Recruiting
        • Research Facility
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Research Facility
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Recruiting
        • Research Facility
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Research Facility
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Research Facility
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Recruiting
        • Research Facility
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Research Facility
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Research Facility
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Recruiting
        • Research Facility
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Research Facility

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age of at least 18 years at the time of signing the informed consent form (ICF)
  • Histologically/cytologically confirmed diagnosis of HCC.
  • Barcelona Clinic Liver Cancer (BCLC) Stage C or BCLC Stage B not amenable to locoregional therapy
  • Child-Pugh A
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS 0-1)
  • Disease progression after 1 prior systemic therapy for unresectable HCC
  • Measurable disease per RECIST v1.1
  • Sufficient renal function
  • Adequate hematologic function
  • Adequate hepatic function
  • The subject must have recovered from toxicities related to prior treatments to ≤Grade 1, unless clinically nonsignificant and/or stable on supportive therapy
  • If HBV or HCV infection: Disease managed per local practice; antiviral treatment is allowed.
  • Gastric or esophageal varices previously treated with endoscopic therapy according to institutional standards are permitted if no clinically significant bleeding

  • For women of childbearing potential (WOCBP):

    • Negative serum pregnancy test within 48 hours prior to the first dose of RYZ811
    • Agreement to use barrier contraception and a second form of highly effective contraception

  • For sexually active males:

    • Must use a condom during intercourse
    • Male subjects whose sexual partners are WOCBP must also agree to use a second form of highly effective contraception
    • A condom is required to be used also by vasectomized men

Exclusion Criteria:

  • Subjects with fibrolamellar carcinoma, sarcomatoid HCC or combined hepatocellular cholangiocarcinoma
  • Prior liver transplantation
  • Known hypersensitivity to 68Ga, 225Ac or any of the excipients of RYZ811 or RYZ801
  • Portal vein tumor thrombosis classified as Vp4
  • Documented hepatic encephalopathy within 6 months of enrollment
  • Clinically meaningful ascites within 6 months of enrollment
  • Prior EBRT to the liver within 12 weeks prior to receiving RYZ811
  • Prior liver radioembolization
  • Previously treated central nervous system (CNS) metastasis without recovery from acute side effects
  • Documented history of idiopathic pulmonary fibrosis (IPF), interstitial lung disease (ILD) or pneumonitis

  • Uncontrolled significant intercurrent illness including, but not limited to:

    • QT interval corrected for heart rate using Fridericia's formula (QTcF) >470 ms
    • Hemoglobin A1c (Hgb A1c) ≥8%
    • Uncontrolled hypertension
    • Dose Expansion only: Prior treatment with lenvatinib is exclusionary
    • Significant cardiovascular disease or heart failure
  • History of clinically significant bleeding
  • Prior participation in any interventional clinical study
  • Current somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study
  • Have a history of primary malignancy within the past 3 years other than (1) HCC, (2) adequately treated carcinoma in situ or non-melanoma carcinoma of the skin, (3) any other curatively treated malignancy that is not expected to require treatment for recurrence during participation in the study, or (4) an untreated cancer on active surveillance that may not affect the subject's survival status for >3 years
  • Subject requires other treatment that in the opinion of the Investigator would be more appropriate than what is offered in the study
  • Pregnancy or breastfeeding

Note: Additional criteria may apply and will be assessed by the study site

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation, Dose Expansion (Dose Optimization/Randomized Phase 2)
Diagnostic test: RYZ811
Ga-68
Drug: RYZ801
Ac-225
Active Comparator: Standard of Care (SoC) (Randomized Phase 2)
Diagnostic test: RYZ811
Ga-68

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Therapeutic - RYZ801
Time Frame: Rate of DLTs during the first 42 days of study treatment
To determine the RTA of RYZ801 in subjects with GPC3+ unresectable HCC (Dose Escalation only)
Rate of DLTs during the first 42 days of study treatment
Therapeutic - RYZ801
Time Frame: From enrollment for up to three months or study discontinuation, whichever occurs first.
To determine if treatment with RYZ801, compared to SoC therapy, improves ORR in subjects with GPC3+ unresectable HCC (Dose Expansion Stage 2 only) using ORR (rate of CR or PR), as determined by BICR according to RECIST v1.1
From enrollment for up to three months or study discontinuation, whichever occurs first.
Therapeutic - RYZ801
Time Frame: From enrollment to 3months after randomization or study discontinuation, whichever occurs first.
To evaluate ORR of RYZ801 different dosing regimens (Dose Expansion Stage 1 only) and determine dosage optimized RP2D using ORR (rate of confirmed CR or PR) by RECIST v1.1 per investigator assessment
From enrollment to 3months after randomization or study discontinuation, whichever occurs first.
Diagnostic - RYZ811
Time Frame: Baseline, pre-injection and post-injection up to 6 days post injection.
To assess the safety and tolerability of RYZ811 in subjects with unresectable HCC. Safety and tolerability of RYZ811 as measured by incidence and severity of AEs, including SAEs, laboratory changes, and other safety findings.
Baseline, pre-injection and post-injection up to 6 days post injection.
Diagnostic - RYZ811
Time Frame: RYZ811 biodistribution to be assessed on the day of injection.
To evaluate the biodistribution of RYZ811 in subjects with unresectable HCC. SUV (mean, maximum and peak) of organs and tumors; volume of RYZ811 avid uptake in tumor lesions; and tumor-to-normal organ tracer uptake ratios.
RYZ811 biodistribution to be assessed on the day of injection.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

RayzeBio, Inc.

Investigators

  • Study Director: Freddy Escorcia, MD, PhD, RayzeBio, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 5, 2025

Primary Completion (Estimated)

June 1, 2030

Study Completion (Estimated)

June 1, 2031

Study Registration Dates

First Submitted

November 5, 2024

First Submitted That Met QC Criteria

December 4, 2024

First Posted (Actual)

December 10, 2024

Study Record Updates

Last Update Posted (Actual)

April 13, 2026

Last Update Submitted That Met QC Criteria

April 6, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RYZ801-101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hepatocellular Carcinoma (HCC)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Malaysia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe