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)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 590
- 试验地点
- 14
- 主要终点
- Therapeutic - RYZ801
研究概览
简要总结
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Blinded Imaging Central Reviewer (BICR) during Randomized Phase 2
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Dose Escalation, Dose Expansion (Dose Optimization/Randomized Phase 2)
干预措施: RYZ801 (Drug)
Dose Escalation, Dose Expansion (Dose Optimization/Randomized Phase 2)
干预措施: RYZ811 (Diagnostic Test)
Standard of Care (SoC) (Randomized Phase 2)
干预措施: RYZ811 (Diagnostic Test)
结局指标
主要结局
Therapeutic - RYZ801
时间窗: Baseline, before and after each RYZ801 treatment cycle. For the Dose Escalation, Cycle 1 is 42 days. All other cycles are 28 days.
To assess the safety and tolerability of RYZ801 in subjects with GPC3+ unresectable HCC. Safety and tolerability of RYZ801 as measured by incidence and severity of AEs, including SAEs, laboratory changes, and other safety findings.
Diagnostic - RYZ811
时间窗: RYZ811 biodistribution to be assessed by PET/CT at 1, 2 and 3 hours post-injection.
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.
Therapeutic - RYZ801
时间窗: 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)
Therapeutic - RYZ801
时间窗: From enrollment for up to three months or study discontinuation, whichever occurs first.
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
Therapeutic - RYZ801
时间窗: From enrollment to 3months after randomization or study discontinuation, whichever occurs first.
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
Diagnostic - RYZ811
时间窗: 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.
Diagnostic - RYZ811
时间窗: RYZ811 biodistribution to be assessed on the day of injection.
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.
次要结局
未报告次要终点