Hepatocellular Carcinoma (HCC)Phase 1/2GPC3NCT06726161
Study of the Theranostic Pair RYZ811 (Diagnostic) and RYZ801 (Therapeutic) to Identify and Treat Subjects With GPC3+ (Glypican-3) Unresectable HCC
A Phase 1/2 study testing RYZ811 and RYZ801 in people with Hepatocellular Carcinoma (HCC), run by RayzeBio, Inc. at 13 sites in United States.
Trial summary
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) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma (HCC)
- What is being tested?
- RYZ811 and RYZ801
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 590 participants
- Where
- 13 sitesUnited States
- Study dates
- 5 Sep 2025to Jun 2031
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
13 sites in 1 country. Contact the study team or a site near you to ask about taking part.
13 sites in 1 country
United States13 sites, 13 recruiting
- Recruiting
Research Facility
Baltimore, Maryland, 21287
- Recruiting
Research Facility
Birmingham, Alabama, 35294
- Recruiting
Research Facility
Charlottesville, Virginia, 22908
- Recruiting
Research Facility
Houston, Texas, 77030
- Recruiting
Research Facility
Jacksonville, Florida, 32224
- Recruiting
Research Facility
Lexington, Kentucky, 40536
- Recruiting
Research Facility
New York, New York, 10065
- Recruiting
Research Facility
Omaha, Nebraska, 68130
- Recruiting
Research Facility
Orange, California, 92868
- Recruiting
Research Facility
Phoenix, Arizona, 85054
- Recruiting
Research Facility
Rochester, Minnesota, 55905
- Recruiting
Research Facility
Seattle, Washington, 98109
- Recruiting
Research Facility
St Louis, Missouri, 63104
About this study
Official title: 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)
- Conditions
- Hepatocellular Carcinoma (HCC)
- Being tested
- RYZ811, RYZ801
- Keywords
- actinium, theranostic, alpha-emitter, RYZ811, RYZ801, 225Ac, HCC, targeted radiotherapy, radiopharmaceutical, unresectable HCC, Rayze, RayzeBio, BMS, Bristol Myers Squibb, RPT, Imaging Agent, Hepatocellular Carcinoma, Diagnostic, GPC3
- Medical subject headings
- Carcinoma, Hepatocellular, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RYZ811Diagnostic test
Ga-68
RYZ801Drug
Ac-225
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation, Dose Expansion (Dose Optimization/Randomized Phase 2) | Experimental | Not described Receives: Diagnostic Test: RYZ811; Drug: RYZ801 |
| Standard of Care (SoC) (Randomized Phase 2) | Active comparator | Not described Receives: Diagnostic Test: RYZ811 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Therapeutic - RYZ801
To determine the RTA of RYZ801 in subjects with GPC3+ unresectable HCC (Dose Escalation only)
Measured: Rate of DLTs during the first 42 days of study treatment
Therapeutic - RYZ801
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
Measured: From enrollment for up to three months or study discontinuation, whichever occurs first.
Therapeutic - RYZ801
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
Measured: From enrollment to 3months after randomization or study discontinuation, whichever occurs first.
Diagnostic - RYZ811
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.
Measured: Baseline, pre-injection and post-injection up to 6 days post injection.
Diagnostic - RYZ811
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.
Measured: RYZ811 biodistribution to be assessed on the day of injection.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2024
- Study start5 Sep 2025
- Primary completionJun 2030 (estimated)
- Study completionJun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular Carcinoma (HCC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Dose escalation, randomized Phase 2 compared to SoC
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 590 participants (estimated)
Sponsor and investigators
- Lead sponsor
- RayzeBio, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Freddy Escorcia, MD, PhD, Study director, RayzeBio, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06726161
- Sponsor's protocol ID
- RYZ801-101
- Acronym
- GPC3
- Status last verified
- Sep 2026
- First submitted
- 5 Nov 2024
- Last updated
- 28 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No