A Randomized Phase 2 Trial of Atezolizumab and Bevacizumab in Combination With SRF388 or Placebo in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 55
- 主要终点
- Progression Free Survival (PFS) according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
研究概览
简要总结
This is a Phase 2 trial composed of an open label Lead-In followed by a Randomized Phase designed to evaluate the efficacy and safety of SRF388 in combination with atezolizumab plus bevacizumab compared to placebo (inactive substance) in combination with atezolizumab plus bevacizumab in patients with first-line advanced or metastatic HCC.
详细描述
This is a Phase 2 trial designed to evaluate the efficacy and safety of SRF388 in combination with atezolizumab plus bevacizumab (Arm A) compared to placebo in combination with atezolizumab plus bevacizumab (Arm B) in patients with first-line advanced or metastatic HCC.
After a Lead-In Phase of up to 30 patients who will receive open-label SRF388 + atezolizumab + bevacizumab, the blinded Randomized Phase will randomize approximately 104 patients with a 1:1 allocation to Arm A or Arm B and stratified by geographic region (Asia excluding Japan vs. rest of world) and Barcelona Clinic Liver Cancer (BCLC) stage (B or C).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Abbreviated Inclusion Criteria:
- •≥ 18 years of age on day of signing informed consent
- •Unresectable locally advanced or metastatic HCC
- •No prior systemic treatment for unresectable locally advanced or metastatic HCC
- •BCLC Stage B or Stage C disease
- •Child-Pugh Class A disease
- •≥ 1 measurable lesion per RECIST v1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Laboratory values indicative of adequate organ function as defined in the protocol
- •Women of childbearing potential must have a negative pregnancy test within 1 week prior to first dose of study drug
- •Women of childbearing potential or men with a heterosexual partner of childbearing potential or pregnant must agree to refrain from sexual intercourse or be willing to use effective methods of contraception as defined in the protocol while receiving study drug and for 6 months after the last dose of any study drug
- •Abbreviated
排除标准
- •Currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
- •Previously received an anti-interleukin (IL)-27 antibody (Ab) or anti-IL-27-targeted therapy.
- •Received prior systemic therapy for unresectable or metastatic disease. (Note: Prior systemic therapies administered for neoadjuvant, adjuvant, or curative intent (localized disease) are permitted if they were given > 1 year prior to the development of recurrent or metastatic disease)
- •Known fibrolamellar HCC histology, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
- •Moderate or severe ascites
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
- •History of or current hepatic encephalopathy
- •Unable to undergo disease evaluation with a triphasic CT or MRI because of contrast allergy or other contraindication
- •Untreated or incompletely treated varices with bleeding or high risk for bleeding.
- •Symptomatic or untreated brain metastases or leptomeningeal carcinomatosis.
- •Active or history of autoimmune disease or immune deficiency with some exceptions such as controlled thyroid disease, Type 1 diabetes, eczema and other minor skin disorders.
- •Medical conditions requiring chronic steroid therapy (ie, > 10 mg/day of prednisone or its equivalent) or anticipates the need for systemic immunosuppressive medications during treatment with study drug
- •Known active infection with HIV
- •Known infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), except for controlled active HBV or fully treated HCV infection as defined by the protocol
- •Inadequately controlled arterial hypertension
研究组 & 干预措施
Arm B: Placebo in combination with atezolizumab plus bevacizumab
Patients randomized to Arm B will receive placebo with atezolizumab plus bevacizumab.
干预措施: Atezolizumab (Drug)
Lead-In
A minimum of 6 patients and up to 30 patients will be enrolled in an open-label Lead-In to assess the preliminary safety and tolerability of SRF388 with atezolizumab plus bevacizumab.
干预措施: SRF388 (Drug)
Lead-In
A minimum of 6 patients and up to 30 patients will be enrolled in an open-label Lead-In to assess the preliminary safety and tolerability of SRF388 with atezolizumab plus bevacizumab.
干预措施: Bevacizumab (Drug)
Lead-In
A minimum of 6 patients and up to 30 patients will be enrolled in an open-label Lead-In to assess the preliminary safety and tolerability of SRF388 with atezolizumab plus bevacizumab.
干预措施: Atezolizumab (Drug)
Arm A: SRF388 in Combination with atezolizumab plus bevacizumab
Patients randomized to Arm A will receive SRF388 with atezolizumab plus bevacizumab.
干预措施: Bevacizumab (Drug)
Arm A: SRF388 in Combination with atezolizumab plus bevacizumab
Patients randomized to Arm A will receive SRF388 with atezolizumab plus bevacizumab.
干预措施: SRF388 (Drug)
Arm A: SRF388 in Combination with atezolizumab plus bevacizumab
Patients randomized to Arm A will receive SRF388 with atezolizumab plus bevacizumab.
干预措施: Atezolizumab (Drug)
Arm B: Placebo in combination with atezolizumab plus bevacizumab
Patients randomized to Arm B will receive placebo with atezolizumab plus bevacizumab.
干预措施: Placebo (Drug)
Arm B: Placebo in combination with atezolizumab plus bevacizumab
Patients randomized to Arm B will receive placebo with atezolizumab plus bevacizumab.
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Progression Free Survival (PFS) according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
时间窗: Up to 2 years
PFS according to RECIST v1.1 will be evaluated in patients receiving SRF388 in combination with atezolizumab plus bevacizumab compared to placebo in combination with atezolizumab plus bevacizumab (Randomized Phase).
Nature, frequency, and severity of adverse events (AEs) per NCI CTCAE version 5.0 or higher
时间窗: Up to 2 years
Summaries of AEs will be based on TEAEs. A TEAE is an AE that emerges or worsens in the period from the first dose of study drug to 30 days after the last dose of study drug (Lead-In Phase).
次要结局
- Duration of Response (DoR) according to RECIST 1.1(Up to 2 years)
- Time to Progression (TTP) according to RECIST v1.1(Up to 2 years)
- Nature, frequency, and severity of adverse events (AEs) per NCI CTCAE version 5.0 or higher(Up to 2 years)
- Incidence of SRF388 Antidrug Antibodies (ADAs)(Up to 2 years)
- Maximum observed serum concentration (Cmax) of SRF388(Up to 2 years)
- PFS according to HCC modified RECIST (mRECIST)(Up to 2 years)
- Duration of Response (DoR) according to HCC mRECIST(Up to 2 years)
- Disease Control Rate (DCR)(Up to 2 years)
- TTP according to mRECIST(Up to 2 years)
- Progression Free Survival (PFS) according to RECIST v1.1(Up to 2 years)
- Objective Response Rate (ORR) according to RECIST v1.1(Up to 2 years)
- ORR according to HCC mRECIST(Up to 2 years)
- Overall Survival (OS)(Up to 2 years)
- Time to Response according to RECIST v1.1(Up to 2 years)
- Time to Response according to HCC mRECIST(Up to 2 years)
- Terminal elimination half-life (t1/2)(Up to 2 years)
- Serum concentrations of atezolizumab(Up to 2 years)
- Incidence of atezolizumab ADAs(Up to 2 years)
- Area under the serum concentration-time curve from time zero to the last quantifiable time point (AUC0-last)(Up to 2 years)
- Time of maximum observed serum concentration (tmax) of SRF388(Up to 2 years)