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

RayzeBio

Status and phase

Enrolling

Phase 1

Conditions

HCC

Treatments

Drug: RYZ801

Diagnostic Test: RYZ811

Study type

Interventional

Funder types

Industry

Identifiers

NCT06726161

RYZ801-101

Details and patient eligibility

About

A single arm, open-label Phase 1/1b study of the theranostic pair RYZ811 (diagnostic) and RYZ801 (therapeutic) to identify and treat subjects with GPC3+ unresectable HCC

Enrollment

70 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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
ECOG PS 0-1
At least 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 or candidates for 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
Clinically meaningful ascites
Prior EBRT to the liver
Prior EBRT to >25% of the bone marrow
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
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