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

NCT06726161 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: RYZ801-101
• Study Type: interventional
• Target: 590
• Locations: 1 country
• Sites: 13

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)

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

Outcome Measures

Primary Outcomes (5)

• Therapeutic - RYZ801

  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

  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

  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

  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

  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.

Study Arms (2)

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

EXPERIMENTAL

Diagnostic Test: RYZ811; Drug: RYZ801

Standard of Care (SoC) (Randomized Phase 2)

ACTIVE COMPARATOR

Diagnostic Test: RYZ811

Interventions

RYZ811 DIAGNOSTIC_TEST

Ga-68

Dose Escalation, Dose Expansion (Dose Optimization/Randomized Phase 2); Standard of Care (SoC) (Randomized Phase 2)

RYZ801 DRUG

Ac-225

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Significant cardiovascular disease or heart failure

Sponsors & Collaborators

• RayzeBio, Inc.: lead

Study Sites (13)

Research Facility

Birmingham, Alabama, 35233, United States

RECRUITING

Research Facility

Phoenix, Arizona, 85054, United States

RECRUITING

Research Facility

Tucson, Arizona, 85719, United States

RECRUITING

Research Facility

Orange, California, 92868, United States

RECRUITING

Research Facility

Jacksonville, Florida, 32224, United States

RECRUITING

Research Facility

Lexington, Kentucky, 40536, United States

RECRUITING

Research Facility

Baltimore, Maryland, 21287, United States

RECRUITING

Research Facility

Rochester, Minnesota, 55905, United States

RECRUITING

Research Facility

Omaha, Nebraska, 68130, United States

RECRUITING

Research Facility

New York, New York, 10065, United States

RECRUITING

Research Facility

Houston, Texas, 77030, United States

RECRUITING

Research Facility

Charlottesville, Virginia, 22908, United States

RECRUITING

Research Facility

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Disease

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Freddy Escorcia, MD, PhD

  RayzeBio, Inc.

  STUDY DIRECTOR

Central Study Contacts

RayzeBio Clinical Trials

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Blinded Imaging Central Reviewer (BICR) during Randomized Phase 2
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation, randomized Phase 2 compared to SoC

Study Record Dates

• First Submitted: November 5, 2024
• First Posted: December 10, 2024
• Study Start: September 5, 2025
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2031
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

US (13)