An Open-Label, Multicenter, Phase 1 Study of Ramucirumab Plus MEDI4736 in Patients With Locally Advanced and Unresectable or Metastatic Gastrointestinal or Thoracic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 85
- 试验地点
- 11
- 主要终点
- Number of Participants with Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The main purpose of this study is to evaluate the safety of ramucirumab plus MEDI4736 in participants with locally advanced and unresectable or metastatic gastrointestinal or thoracic malignancies including gastric or gastroesophageal junction (GEJ) adenocarcinoma, non-small cell lung cancer (NSCLC), or hepatocellular carcinoma (HCC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •Measurable metastatic disease or locally advanced and unresectable disease
- •Has histopathologically confirmed gastric or GEJ adenocarcinoma with documented disease progression after 1-2 prior lines of systemic therapy
- •Has histopathologically confirmed nonsquamous or squamous NSCLC with documented disease progression after 1-3 prior lines of systemic therapy
- •Has histopathologically or cytologically confirmed HCC, Child-Pugh Class A, with documented disease progression during or after discontinuation of sorafenib therapy, or intolerance of sorafenib therapy, and an α-fetoprotein (AFP) ≥ 1.5x upper limit of normal
- •Availability of tumor tissue for biomarker analysis
- •Has an Eastern Cooperative Oncology Group Performance Status of 0 or 1
- •Has adequate organ function
排除标准
- •Has known brain metastases
- •Has a history of prior cancers not included in this study that were either not treated with curative intent or have been active within the past 5 years
- •History of allogeneic organ transplant
- •Has active or prior documented autoimmune disease within the past 24 months
- •Has human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness, or a history of immunodeficiency
- •Has active hepatitis B or hepatitis C infection, or co-infection with both hepatitis B and C virus
- •For gastric/GEJ and NSCLC participants, has chronic hepatitis B or hepatitis C infection. (For HCC participants, those with chronic hepatitis B virus [HBV] infection with a negative HBV deoxyribonucleic acid [DNA] test and who are on antiviral therapy, and those with chronic hepatitis C virus [HCV] infection are eligible)
- •Has a history of interstitial lung disease, idiopathic pulmonary fibrosis, pneumoconiosis, non-infections pneumonitis, radiation-induced or drug-induced pneumonitis
- •Has received any previous systemic therapy targeting programmed death (PD) 1 or PD-ligand 1/2 signaling pathways, and other immune checkpoint inhibitors
- •Have received previous systemic therapy with ramucirumab
研究组 & 干预措施
Ramucirumab + MEDI4736 (NSCLC)
In phase 1a (DLT phase), ramucirumab plus MEDI4736 given intravenously (IV) every 3 weeks (q3w) of a 21 day treatment cycle. Participants may continue to receive study treatment until discontinuation criteria are met.
In phase 1b (expansion phase), ramucirumab plus MEDI4736 given IV q3w. Participants may continue to receive study treatment until discontinuation criteria are met.
干预措施: Ramucirumab (Drug)
Ramucirumab + MEDI4736 (NSCLC)
In phase 1a (DLT phase), ramucirumab plus MEDI4736 given intravenously (IV) every 3 weeks (q3w) of a 21 day treatment cycle. Participants may continue to receive study treatment until discontinuation criteria are met.
In phase 1b (expansion phase), ramucirumab plus MEDI4736 given IV q3w. Participants may continue to receive study treatment until discontinuation criteria are met.
干预措施: MEDI4736 (Drug)
Ramucirumab + MEDI4736 (Gastric/GEJ)
In phase 1a (DLT phase), ramucirumab plus MEDI4736 given IV every 2 weeks (q2w) of a 28 day treatment cycle. Participants may continue to receive study treatment until discontinuation criteria are met.
In phase 1b (expansion phase), ramucirumab plus MEDI4736 given IV q2w. Participants may continue to receive study treatment until discontinuation criteria are met.
干预措施: Ramucirumab (Drug)
Ramucirumab + MEDI4736 (Gastric/GEJ)
In phase 1a (DLT phase), ramucirumab plus MEDI4736 given IV every 2 weeks (q2w) of a 28 day treatment cycle. Participants may continue to receive study treatment until discontinuation criteria are met.
In phase 1b (expansion phase), ramucirumab plus MEDI4736 given IV q2w. Participants may continue to receive study treatment until discontinuation criteria are met.
干预措施: MEDI4736 (Drug)
Ramucirumab + MEDI4736 (HCC)
In phase 1a (DLT phase), ramucirumab plus MEDI4736 given IV q2w of a 28 day treatment cycle. Participants may continue to receive study treatment until discontinuation criteria are met.
In phase 1b (expansion phase), ramucirumab plus MEDI4736 given IV q2w. Participants may continue to receive study treatment until discontinuation criteria are met.
干预措施: Ramucirumab (Drug)
Ramucirumab + MEDI4736 (HCC)
In phase 1a (DLT phase), ramucirumab plus MEDI4736 given IV q2w of a 28 day treatment cycle. Participants may continue to receive study treatment until discontinuation criteria are met.
In phase 1b (expansion phase), ramucirumab plus MEDI4736 given IV q2w. Participants may continue to receive study treatment until discontinuation criteria are met.
干预措施: MEDI4736 (Drug)
结局指标
主要结局
Number of Participants with Dose Limiting Toxicities (DLTs)
时间窗: Cycle 1 (up to 28 days)
次要结局
- Proportion of Participants with a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)(Baseline to Disease Progression (Approximately 22 Months))
- Number of Participants with Treatment Emergent Anti Ramucirumab Antibodies(Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months))
- Percentage of Participants with a Best Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)(Baseline to Disease Progression (Approximately 22 Months))
- Duration of Response (DoR)(Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Approximately 22 Months))
- Number of Participants with Treatment Emergent Anti MEDI4736 Antibodies(Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months))
- Overall Survival (OS)(Baseline to Progressive Disease or Death from Any Cause (Approximately 32 Months))
- Time to First Response (TTR)(Baseline to Date of CR or PR (Approximately 22 Months))
- Progression Free Survival (PFS)(Baseline to Progressive Disease or Death from Any Cause (Approximately 22 Months))
- Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab and MEDI4736(Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months))
- PK: Minimum Concentration (Cmin) of Ramucirumab and MEDI4736(Predose Cycle 1 Day 1 through Follow up (Approximately 22 Months))