A Randomized, Phase 1b/2 Trial of AMG 102 or AMG 479 in Combination With Panitumumab Versus Panitumumab Alone in Subject With Wild-Type KRAS Metastatic Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 177
- 主要终点
- Part 2: Percentage of Participants With an Objective Response
研究概览
简要总结
This study is a global, multicenter, open-label phase 1b and randomized, double-blinded, 2 part, phase 2 study designed to evaluate the safety and efficacy of rilotumumab or ganitumab in combination with panitumumab versus panitumumab alone in patients with metastatic colorectal cancer whose tumors are wild-type KRAS status.
详细描述
This study consisted of 3 parts:
Part 1: determination of the tolerable dose of rilotumumab in combination with panitumumab to be administered in Part 2.
Part 2: Comparison of the safety and efficacy of rilotumumab or ganitumab in combination with panitumumab versus that of panitumumab alone. In Part 2, participants were randomized 1:1:1 into 3 cohorts: 6 mg/kg panitumumab plus 10 mg/kg rilotumumab, 6 mg/kg panitumumab plus 12 mg/kg ganitumab, or 6 mg/kg panitumumab and placebo (panitumumab alone cohort). Panitumumab was administered open-label, and rilotumumab and ganitumab were double-blinded.
Part 3: Exploratory evaluation of the safety and efficacy of the rilotumumab and ganitumab monotherapy following treatment with panitumumab in Part 2. In Part 3, eligible participants who terminated panitumumab treatment in the Panitumumab Alone arm of Part 2 due to disease progression or intolerability could be randomized 1:1 into 2 double-blind cohorts: 10 mg/kg rilotumumab or 12 mg/kg ganitumab.
Participants who permanently discontinued all the investigational products completed a safety follow-up visit 30 days and a follow-up visit 60 days after the last dose of investigational product. Participants were followed for radiographic disease progression and survival every 3 months after the 30-day safety follow-up visit for up to 2 years after the last participant was enrolled in Part 2.
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)
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
- •metastatic adenocarcinoma of the colon or rectum
- •wild-type KRAS tumor status
- •radiographic evidence of disease progression during or following treatment with irinotecan and/or oxaliplatin containing chemotherapy for mCRC
- •measurable disease >/= 20 mm per Response Evaluation Criteria In Solid Tumors (RECIST)
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •adequate laboratory values
排除标准
- •history of central nervous system (CNS) metastases
- •history of another primary cancer, unless:
- •curatively resected non-melanomatous skin cancer
- •curatively treated cervical carcinoma in situ
- •other primary solid tumor treated with curative intent and no known active disease present for >/= 5 years
- •prior treatment with an anti-epithelial growth factor receptor (EGFR), hepatocyte growth factor receptor (HGFR, c-MET), and/or insulin-like growth factor receptor (IGFR) inhibitor
- •prior treatment with AMG 102 or AMG 479
- •prior treatment with chemotherapy or radiotherapy </= 21 days
- •prior treatment with targeted therapy </= 30 days
- •known allergy or hypersensitivity to panitumumab, AMG 102, or AMG 479
- •history of interstitial lung disease
- •clinically significant cardiovascular disease </= 1 year
- •active inflammatory bowel disease
- •known human immunodeficiency virus (HIV), hepatitis C, or hepatitis B infection
- •any co-morbid disease or condition that could increase the risk of toxicity
- •serious or non-healing wound </= 35 days
- •any uncontrolled concurrent illness or history of any medical condition that could interfere with the interpretation of the study results
- •major surgical procedure </= 35 days or minor surgical procedure </= 14 days
- •other investigational procedures or drugs </= 30 days
研究组 & 干预措施
Part 1: Panitumumab + Rilotumumab
Participants received panitumumab 6 mg/kg and rilotumumab 10 mg/kg by intravenous infusion once every 2 weeks until progressive disease, intolerability, withdrawal, death or sponsor decision.
干预措施: Panitumumab (Drug)
Part 1: Panitumumab + Rilotumumab
Participants received panitumumab 6 mg/kg and rilotumumab 10 mg/kg by intravenous infusion once every 2 weeks until progressive disease, intolerability, withdrawal, death or sponsor decision.
干预措施: Rilotumumab (Drug)
Part 2: Panitumumab Alone
Participants received panitumumab 6 mg/kg and placebo by intravenous infusion once every 2 weeks until progressive disease, intolerability, withdrawal, death or sponsor decision.
干预措施: Panitumumab (Drug)
Part 2: Panitumumab + Rilotumumab
Participants received panitumumab 6 mg/kg and rilotumumab 10 mg/kg by intravenous infusion once every 2 weeks until progressive disease, intolerability, withdrawal, death or sponsor decision.
干预措施: Panitumumab (Drug)
Part 2: Panitumumab + Rilotumumab
Participants received panitumumab 6 mg/kg and rilotumumab 10 mg/kg by intravenous infusion once every 2 weeks until progressive disease, intolerability, withdrawal, death or sponsor decision.
干预措施: Rilotumumab (Drug)
Part 2: Panitumumab + Rilotumumab
Participants received panitumumab 6 mg/kg and rilotumumab 10 mg/kg by intravenous infusion once every 2 weeks until progressive disease, intolerability, withdrawal, death or sponsor decision.
干预措施: Placebo (Drug)
Part 2: Panitumumab + Ganitumab
Participants received panitumumab 6 mg/kg and ganitumab 12 mg/kg by intravenous infusion once every 2 weeks until progressive disease, intolerability, withdrawal, death or sponsor decision.
干预措施: Panitumumab (Drug)
Part 2: Panitumumab + Ganitumab
Participants received panitumumab 6 mg/kg and ganitumab 12 mg/kg by intravenous infusion once every 2 weeks until progressive disease, intolerability, withdrawal, death or sponsor decision.
干预措施: Ganitumab (Drug)
Part 2: Panitumumab + Ganitumab
Participants received panitumumab 6 mg/kg and ganitumab 12 mg/kg by intravenous infusion once every 2 weeks until progressive disease, intolerability, withdrawal, death or sponsor decision.
干预措施: Placebo (Drug)
Part 3: Rilotumumab
Participants randomized to Panitumumab Alone in Part 2 who had disease progression (radiographic or clinical) or intolerability were re-randomized in Part 3 to receive rilotumumab 10 mg/kg every 2 weeks until disease progression, intolerability, withdrawal, death, or sponsor decision.
干预措施: Rilotumumab (Drug)
Part 3: Rilotumumab
Participants randomized to Panitumumab Alone in Part 2 who had disease progression (radiographic or clinical) or intolerability were re-randomized in Part 3 to receive rilotumumab 10 mg/kg every 2 weeks until disease progression, intolerability, withdrawal, death, or sponsor decision.
干预措施: Placebo (Drug)
Part 3: Ganitumab
Participants randomized to Panitumumab Alone in Part 2 who had disease progression (radiographic or clinical) or intolerability were re-randomized in Part 3 to receive ganitumab 12 mg/kg every 2 weeks until disease progression, intolerability, withdrawal, death, or sponsor decision.
干预措施: Ganitumab (Drug)
Part 3: Ganitumab
Participants randomized to Panitumumab Alone in Part 2 who had disease progression (radiographic or clinical) or intolerability were re-randomized in Part 3 to receive ganitumab 12 mg/kg every 2 weeks until disease progression, intolerability, withdrawal, death, or sponsor decision.
干预措施: Placebo (Drug)
结局指标
主要结局
Part 2: Percentage of Participants With an Objective Response
时间窗: From the date of first dose until the data cut-off date of 23 July 2010. Median follow-up time was 30 weeks.
An objective response is defined as a confirmed complete (CR) or partial response (PR) no less than 4 weeks after the criteria for response are first met, determined by the investigator considering the radiologic response of all existing target and non-target lesions, evidence of new lesions, and cytology evaluation (as appropriate) according to the Modified-Response Evaluation Criteria In Solid Tumors (RECIST) v1.0 criteria: CR: Disappearance of all target and non-target and no new lesions. PR: At least a 30% decrease in the size of target lesions with no increase in non-target lesions, or, the disappearance of all target lesions and persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease. Participants without a post-baseline assessment were considered non-responders. Tumor assessments up to the initiation of another anti-tumor therapy including the Part 3 treatment, if applicable, were used.
Part 1: Number of Participants With Dose-limiting Toxicities (DLT)
时间窗: 7 weeks
A DLT is defined as any grade 3 or 4 rilotumumab-related or combination (panitumumab and rilotumumab)-related adverse event or laboratory abnormality that is deemed clinically significant by the investigator
次要结局
- Cmin, Cmax of Panitumumab(14 days)
- Cmax for Ganitumab - Part 2(Up to 23 weeks)
- Duration of Response - Part 2(From the date of first dose until the data cut-off date of 23 July 2010. Median follow-up time was 30 weeks.)
- Disease Control Rate - Part 2(From the date of first dose until the data cut-off date of 23 July 2010. Median follow-up time was 30 weeks.)
- On-treatment Progression-free Survival (PFS) - Part 2(From the date of first dose until the data cut-off date of 23 July 2010. Up to 56 weeks.)
- Cmin for Panitumumab - Part 2(Up to 23 weeks)
- Cmax for Panitumumab - Part 2(Up to 23 weeks)
- Cmin for Rilotumumab - Part 2(Up to 23 weeks)
- Cmin, Cmax, for Rilotumumab(14 days)
- Cmax for Rilotumumab - Part 2(Up to 23 weeks)
- Time to Response - Part 2(From the date of first dose until the data cut-off date of 23 July 2010. Median follow-up time was 30 weeks.)
- Total Anti-AMG 102 Antibody Incidence - Part 2(First dose of any study drug and before 120 days of last dose of study drugs, up to 1 year, eight months.)
- Progression-free Survival (PFS) - Part 2(From the date of first dose until the data cut-off date of 23 July 2010. Median follow-up time was 30 weeks.)
- Overall Survival - Part 2(From the date of first dose until the data cut-off date of 23 July 2010. Median follow-up time was 30 weeks.)
- AUC for Panitumumab(14 Days)
- Total Anti-Panitumumab Antibody Incidence - Part 2(First dose of any study drug and before 120 days of last dose of study drugs; up to 1 year, eight months)
- Cmin for Ganitumab - Part 2(Up to 23 weeks)
- Total Anti-AMG 479 Antibody Incidence - Part 2(First dose of any study drug and before 120 days of last dose of study drugs, up to 1 year, eight months.)
- AUC for Rilotumumab(14 Days)