A Phase 2b, Randomized, Blinded Trial Investigating the Efficacy and Safety of Visugromab in Combination With Nivolumab and Lenvatinib Compared to Double Placebo and Lenvatinib in Participants With Unresectable or Metastatic Hepatocellular Carcinoma and Compensated Liver Function (Child-Pugh A) After Failure of First-Line Treatment That Included an Approved Anti PD-(L)1 Compound (GDFATHER HCC-01)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- CatalYm GmbH
- 入组人数
- 104
- 试验地点
- 14
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
This is a Phase 2b, randomized, blinded clinical trial investigating the efficacy and safety of visugromab in combination with nivolumab and Lenvatinib compared to double placebo and Lenvatinib in participants with unresectable or metastatic HCC and compensated liver function (Child-Pugh A) after failure of 1L treatment that included an anti-PD-(L)1 compound. The trial consists of 2 Parts: a non-randomized Safety-run-in part (Part 1) and the subsequent randomized part (Part 2) with 2 treatment arms (A and B). Randomization of participants into Treatment Arm A and B will continue until 40 efficacy-evaluable participants are enrolled into each Treatment Arm.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Throughout the randomized, blinded, placebo-controlled part (Part 2) of the trial, the participants, Investigators, and trial assigned site staff (except for the pharmacists), the clinical CRO (except for the unblinded clinical monitoring team), and imaging vendor will remain blinded to the information which participant is receiving which IMP. The biostatistics provider, central laboratory vendor, safety vendor and Sponsor also remain blinded.
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Main Inclusion Criteria:
- •Histologically confirmed diagnosis of unresectable or metastatic HCC, not amenable to a curative treatment approach.
- •Measurable disease as per RECIST v1.1 as determined by the Investigator based upon local radiologist assessment.
- •Must have failed one line of prior systemic treatment for unresectable or metastatic HCC containing an approved anti PD (L)-1 checkpoint inhibitor (CPI) with a minimum treatment duration of 12 weeks exposure for the CPI with no documented progression in this period.
- •Age ≥ 18 years on the day of signing the informed consent.
- •Life expectancy of at least 3 months as assessed by the Investigator.
- •ECOG performance status ≤
- •Child-Pugh score of A6 or better.
排除标准
- •Known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma.
- •More than 1 line of prior systemic treatment for unresectable or metastatic HCC.
- •Received or completed any palliative radiotherapy for symptoms within 28 days of the first dose of IMP.
- •Expected to require any other form of antineoplastic therapy during the trial.
- •Clinically active inflammatory bowel disease, active diverticulitis, intra-abdominal abscess, and/or gastrointestinal obstruction.
- •Known history of other prior malignancy unless participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
- •Known or detected clinically active central nervous system (CNS) involvement by HCC or other tumors.
- •Have one of the following cardiovascular risk factors: myocardial infarction, peri/myocarditis, or history of ischemic stroke in the past 3 months before planned treatment start, uncontrolled heart failure, uncontrolled ventricular arrhythmia, QT interval corrected for heart rate using Fridericia's formula interval ≥ 470 ms regardless of sex.
- •An active autoimmune disease that has required systemic treatment in past 3 months before planned treatment start.
- •Comedication with metformin or metformin-containing antidiabetics in participants with type II diabetes.
- •Chronic systemic corticosteroid treatment for other reasons.
- •Prior liver or other organ transplantation.
研究组 & 干预措施
Arm A
Visugromab (IV) + Nivolumab intravenous (IV) + Lenvatinib (PO)
干预措施: Nivolumab (Biological)
Arm A
Visugromab (IV) + Nivolumab intravenous (IV) + Lenvatinib (PO)
干预措施: Visugromab RDE (recommended dose for expansion) (Biological)
Arm A
Visugromab (IV) + Nivolumab intravenous (IV) + Lenvatinib (PO)
干预措施: Lenvatinib (Drug)
Arm B
Lenvatinib (PO) + saline (double-placebo) intravenous (IV)
干预措施: Lenvatinib (Drug)
Arm B
Lenvatinib (PO) + saline (double-placebo) intravenous (IV)
干预措施: Placebo Saline Infusion (Other)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: up to 36 months
Investigator assessed Progression-free survival (PFS) time from randomization (during Safety Run-In: initiation of treatment) to first documented disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred first.
次要结局
- Change in body weight (kg) from baseline(up to 39 months)
- European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score [0-100](up to 39 months)
- Participant weight course over time(up to 39 months)
- Overall survival (OS)(up to 60 months)
- CR (Complete Response) rate(up to 36 months)
- PFS (Progression-free survival) rate(up to 36 months)
- Independently assessed PFS by Blinded Independent Central Review (BICR)(up to 36 months)
- PR (Partial Response) rate(up to 36 months)
- ORR (Overall Response) rate(up to 36 months)
- TTR (Time-to-response) rate(up to 36 months)
- Adverse Events(up to 60 months)
- European Organization for Research and Treatment of Cancer quality-of-life questionnaire for cancer (EORTC QLQ-C30)(up to 39 months)