Hepatocellular Carcinoma (HCC)
Conditions
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
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)
Interventions
DIAGNOSTIC_TESTRYZ811
Ga-68
DRUGRYZ801
Ac-225
Sponsors
RayzeBio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Blinded Imaging Central Reviewer (BICR) during Randomized Phase 2
Intervention model description
Dose escalation, randomized Phase 2 compared to SoC
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Therapeutic - RYZ801 | 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) |
| Diagnostic - RYZ811 | 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. |
Countries
United States
Contacts
CONTACTRayzeBio Clinical Trials
STUDY_DIRECTORFreddy Escorcia, MD, PhD
RayzeBio, Inc.
Outcome results
None listed