Recruiting
Phase 1
Phase 2

RYZ811 & RYZ801

Sponsor:

RayzeBio, Inc.

Code:

NCT06726161

Conditions

Hepatocellular Carcinoma (HCC)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

RYZ811

RYZ801

Study Details

Brief 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)

Conditions

Hepatocellular Carcinoma (HCC)

Study ID

NCT06726161

Start date

Sep 5, 2025

Status verified date

Apr, 2026

Completion date

Jun, 2031

Anticipated

Primary completion date

Jun, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

590 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Dose Escalation, Dose Expansion (Dose Optimization/Randomized Phase 2)

active comparator: Standard of Care (SoC) (Randomized Phase 2)

Interventions

RYZ811

Ga-68

RYZ801

Ac-225

Primary outcome measure

  • Therapeutic - RYZ801 [ Time Frame: 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. ]
  • Therapeutic - RYZ801 [ Time Frame: 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. ]
  • Diagnostic - RYZ811 [ Time Frame: RYZ811 biodistribution to be assessed on the day of injection. ]

Central Contacts and Locations

Central contacts

RayzeBio Clinical Trials

1-619-657-0057clinicaltrials@rayzebio.com

Locations

Research Facility

Recruiting

Birmingham, Alabama, United States, 35233

Research Facility

Recruiting

Phoenix, Arizona, United States, 85054

Research Facility

Recruiting

Tucson, Arizona, United States, 85719

Research Facility

Recruiting

Orange, California, United States, 92868

Research Facility

Recruiting

Jacksonville, Florida, United States, 32224

Research Facility

Recruiting

Lexington, Kentucky, United States, 40536

Research Facility

Recruiting

Baltimore, Maryland, United States, 21287

Research Facility

Recruiting

Rochester, Minnesota, United States, 55905

Research Facility

Recruiting

Omaha, Nebraska, United States, 68130

Research Facility

Recruiting

New York, New York, United States, 10065

Research Facility

Recruiting

Houston, Texas, United States, 77030

Research Facility

Recruiting

Charlottesville, Virginia, United States, 22908

Research Facility

Recruiting

Seattle, Washington, United States, 98109

More Information

Sponsor

RayzeBio, Inc.

Last update posted

Apr 13, 2026

Last verified

Apr, 2026

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by RayzeBio, Inc. on 2026-04-13.