An Open-Label, Multicenter, Phase 1 Study of Ramucirumab Plus Pembrolizumab in Patients With Locally Advanced and Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma, Non-Small Cell Lung Cancer, Transitional Cell Carcinoma of the Urothelium, or Biliary Tract Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 175
- 试验地点
- 7
- 主要终点
- Phase 1a: Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
The main purpose of this study is to evaluate the safety and preliminary efficacy of the combination of the study drug known as ramucirumab plus pembrolizumab in participants with locally advanced and unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, non-small cell lung cancer (NSCLC), transitional cell carcinoma of the urothelium, or biliary tract cancer (BTC).
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
- •Metastatic disease or locally advanced, unresectable disease.
- •Has histopathologically confirmed gastric or GEJ adenocarcinoma with documented disease progression after 0-2 prior lines of systemic therapy
- •Has histopathologically confirmed nonsquamous or squamous NSCLC with documented disease progression after 0-3 prior lines of systemic therapy
- •Has histopathologically confirmed transitional cell carcinoma of the urothelium (bladder, urethra, or renal pelvis) with documented disease progression after 1-3 prior lines of systemic therapy
- •Has histologically confirmed biliary tract adenocarcinoma with documented progression after 1-2 prior lines of systemic therapy
- •Availability of tumor tissue for biomarker analysis from a newly obtained core or excisional biopsy or willing to undergo a tumor biopsy. For first line NSCLC participants only, PD-L1 expression should be 1% or higher.
- •Have an Eastern Cooperative Oncology Group Performance Status of 0 or
- •Has adequate organ function.
- •Have an anticipated life expectancy of ≥3 months.
排除标准
- •Have known brain metastases.
- •Has received ≥3 lines of prior systemic therapy for gastric or GEJ adenocarcinoma and BTC or ≥4 lines for NSCLC or urothelial cancer.
- •Has active autoimmune disease.
- •Known human immunodeficiency virus (HIV) infection.
- •Known active hepatitis B or hepatitis C infection.
- •Has received any previous systemic therapy targeting vascular endothelial growth factor (VEGF) or VEGF receptor, or programmed death (PD) 1 or PD-ligand 1/2 signaling pathways.
- •Have received a live vaccine within 30 days prior to enrollment. Seasonal flu vaccines that do not contain live virus are permitted.
- •Have had a serious or non-healing wound, ulcer, or bone fracture within 28 days prior to enrollment.
- •Have an elective or a planned major surgery during the course of the trial or has undergone major surgery within 28 days prior to enrollment.
研究组 & 干预措施
Cohort A
Participants with gastroesophageal junction (GEJ) cancer [Second-Third Line (L)] received 8 milligrams per kilogram (mg/kg) ramucirumab given intravenously (IV) on day 1 and 8 in combination with 200 mg pembrolizumab given IV on day 1 for every 3 weeks (Q3W) of a 21-day cycle.
干预措施: Ramucirumab (Drug)
Cohort A
Participants with gastroesophageal junction (GEJ) cancer [Second-Third Line (L)] received 8 milligrams per kilogram (mg/kg) ramucirumab given intravenously (IV) on day 1 and 8 in combination with 200 mg pembrolizumab given IV on day 1 for every 3 weeks (Q3W) of a 21-day cycle.
干预措施: Pembrolizumab (Drug)
Cohort D
Participants with Urothelial cancer (Second-Fourth L) received 10 mg/kg ramucirumab given IV on day 1 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.
干预措施: Pembrolizumab (Drug)
Cohort A1
Participants with BTC cancer (Second-Third L) received 8 mg/kg ramucirumab given IV on day 1 and 8 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.
干预措施: Ramucirumab (Drug)
Cohort A2
Participants with Gastric-GEJ cancer (First L) received 8 mg/kg ramucirumab given IV on day 1 and 8 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.
干预措施: Ramucirumab (Drug)
Cohort A2
Participants with Gastric-GEJ cancer (First L) received 8 mg/kg ramucirumab given IV on day 1 and 8 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.
干预措施: Pembrolizumab (Drug)
Cohort B
Participants with Gastric-GEJ cancer (Second-Third L) received 10 mg/kg ramucirumab given IV on day 1 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.
干预措施: Ramucirumab (Drug)
Cohort B
Participants with Gastric-GEJ cancer (Second-Third L) received 10 mg/kg ramucirumab given IV on day 1 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.
干预措施: Pembrolizumab (Drug)
Cohort C
Participants with NSCLC (Second-Fourth L) received 10 mg/kg ramucirumab given IV on day 1 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.
干预措施: Ramucirumab (Drug)
Cohort C
Participants with NSCLC (Second-Fourth L) received 10 mg/kg ramucirumab given IV on day 1 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.
干预措施: Pembrolizumab (Drug)
Cohort D
Participants with Urothelial cancer (Second-Fourth L) received 10 mg/kg ramucirumab given IV on day 1 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.
干预措施: Ramucirumab (Drug)
Cohort E
Participants with NSCLC cancer (First L) received 10 mg/kg ramucirumab given IV on day 1 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.
干预措施: Ramucirumab (Drug)
Cohort E
Participants with NSCLC cancer (First L) received 10 mg/kg ramucirumab given IV on day 1 in combination with 200 mg pembrolizumab given IV on day 1 Q3W of a 21-day cycle.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Phase 1a: Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
时间窗: Cycle 1 (21 Days)
DLT is defined as an Adverse Event (AE) that is likely related to study medication or combination,and fulfills any one of following criteria:Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0): Grade (Gr) 3 and 4 nonlaboratory toxicity (tox),Any Gr 3 or 4 laboratory value if medical intervention is required to treat participant (pt) or abnormality persists for \>1 week;Hematologic tox:Gr 4 toxicity lasting ≥ 7 days,or Gr 3 thrombocytopenia if associated with bleeding and requires platelet transfusion,or Febrile neutropenia Gr 3 or Gr 4;GR 5 tox (death);Any toxicity that is possibly related to study treatment that requires withdrawal of pt from study during Cycle 1,A delay of \> 14 days due to persistent Grade ≥ 2 toxicities in initiating Cycle 2,with exception of Grade 2 fatigue;Any infusion or hypersensitivity reactions are NOT a DLT. A summary of other nonserious AEs and all Serious AEs,regardless of causality is located in Reported Adverse Event section.
次要结局
- Phase 1a and 1b: Progression Free Survival (PFS)(Baseline to PD or Death of Any Cause (Up to 24 Months))
- Phase 1a and 1b: Percentage of Participants Who Achieve Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)](Baseline to Measured Progressive Disease (Up to 24 Months))
- Phase 1a and 1b: Percentage of Participants Who Exhibit Stable Disease (SD) or CR or PR [Disease Control Rate (DCR)](Baseline to Measured Progressive Disease (Up to 24 Months))
- Phase 1a and 1b: Duration of Response (DoR)(Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 24 Months))
- Phase 1a and 1b: Time to First Response (TTR)(Baseline to Date of CR or PR (Up to 24 Months))
- Phase 1a and 1b: Overall Survival (OS)(Baseline to Death from Any Cause (Up to 24 Months))
- Phase 1a and 1b: Pharmacokinetics (PK): Minimum Trough Concentration (Cmin) of Ramucirumab(Phase 1a (Gastric-GEJ or BTC participants (pts)): Week (Wk) 1, 3, 6 and 9; Phase 1a (Gastric, NSCLC, or urothelial pts): Wk 3, 6, 9 and 12; Cohort A, A1, A2: Wk 1, 3, 6, 9, 12, 18, 19 and 24; Cohort B,C,D,E: Wk 3, 6, 9, 12, 18, 19 and 24)