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An Open-Label, Dose-Escalation Study of IMC-20D7S In Participants With Malignant Melanoma

2019年3月11日 更新者：Eli Lilly and Company

An Open-Label, Dose-Escalation Phase 1/1b Study of the Anti-gp75 Monoclonal Antibody IMC-20D7S In Patients With Malignant Melanoma Who Have Progressed After or During at Least One Treatment With Standard Cytotoxic Treatment or/and Immunotherapy Therapy or For Whom Standard Therapy is Not Indicated

A dose-escalation study designed to determine the safety, maximum tolerated dose (MTD), anti-melanoma activity, antibody blood levels and progression-free survival (PFS) in participants with malignant melanoma receiving IMC-20D7S either every 2 weeks or every 3 weeks.

研究概览

地位

完全的

条件

干预/治疗

研究类型

介入性

注册 (实际的)

27

阶段

  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 美国
    • Massachusetts
      • Boston、Massachusetts、美国、02114
        • ImClone Investigational Site
    • New York
      • New York、New York、美国、10021
        • ImClone Investigational Site

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Participant has histologically or cytologically confirmed cutaneous, mucosal, or uveal malignant melanoma which has progressed after or during at least 1 treatment with standard cytotoxic treatment or/and immunotherapy [for example (e.g.), treatment with cytokines, monoclonal antibodies, and vaccines] and is not regarded to be a candidate for a potentially curative, higher priority treatment for melanoma
  • Participant is ≥18 years of age
  • Participant has either measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or evaluable disease
  • At least 21 days must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy. Relative to participant's treatment with non-approved biological products (eg, monoclonal antibodies), a minimum of 2 half-lives must have passed for eligibility to be considered
  • Participant has resolution of all clinically significant toxic effects of prior cancer therapy to Grade ≤1 according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.02 (NCI-CTCAE v4.02)
  • Participant has adequate hematological function, hepatic function, and renal function

Exclusion Criteria:

  • Participant has undergone major surgery [e.g., laparotomy, thoracotomy, removal of organ(s)] within 21 days prior to study entry
  • Participant has elective or planned surgery to be conducted during the trial
  • Participant has documented and/or symptomatic brain or leptomeningeal metastases
  • Participant is receiving systemic steroids or other immunosuppressive medications. (Intermittent use of steroid-containing medications e.g., for asthma exacerbation or for skin lesions is permitted)
  • Participant has an uncontrolled undercurrent illness
  • Participant has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer or other noninvasive carcinoma or in situ neoplasm
  • Participant has a known allergy to any of the treatment components (monoclonal antibodies or other therapeutic proteins such as fresh frozen plasma, human serum albumin, cytokines, or interleukins). In the event that there is suspicion the participant may have allergies, the participant should be excluded
  • Participant is pregnant or lactating
  • Participant has known human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS) infection

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：非随机化
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：IMC-20D7S (1A-4A Cohorts)
Escalating doses up to 30 milligrams per kilogram (mg/kg) administered intravenously (i.v.) every 2 weeks; includes Cohorts 1A, 2A, 3A, and 4A.
生物：IMC-20D7S (Cohort 1A)

5 mg/kg i.v. every 2 weeks.

Administered every other week on Days 1 and 15 of each treatment cycle.

If no dose-limiting toxicity (DLT) in first 3 participants or 1 DLT in 6 participants, then enrollment into Cohort 2A.

其他名称：
  • LY3012215
生物：IMC-20D7S (Cohort 2A)

10 mg/kg i.v. every 2 weeks.

Administered every other week on Days 1 and 15 of each treatment cycle.

If no DLT in first 3 participants or 1 DLT in 6 participants in Cohort 2A, then enrollment into Cohort 3A.

其他名称：
  • LY3012215
生物：IMC-20D7S (Cohort 3A)

20 mg/kg i.v. every 2 weeks.

Administered every other week on Days 1 and 15 of each treatment cycle.

If no DLT in first 3 participants or 1 DLT in 6 participants in Cohort 3A, then enrollment into Cohort 4A.

其他名称：
  • LY3012215
生物：IMC-20D7S (Cohort 4A)

30 mg/kg i.v. every 2 weeks.

Administered every other week on Days 1 and 15 of each treatment cycle.

其他名称：
  • LY3012215
实验性的：IMC-20D7S (1B-3B Cohorts)
Escalating doses up to 30 mg/kg administered i.v. every 3 weeks; includes Cohorts 1B, 2B, and 3B.
生物：IMC-20D7S (Cohort 1B)

10 mg/kg i.v. every 3 weeks.

Administered every 3 weeks on Days 1 and 22 of each treatment cycle.

If no dose-limiting toxicity (DLT) in first 3 participants or 1 DLT in 6 participants in Cohort 1B, then enrollment into Cohort 2B.

其他名称：
  • LY3012215
生物：IMC-20D7S (Cohort 2B)

20 mg/kg i.v. every 3 weeks.

Administered every 3 weeks on Days 1 and 22 of each treatment cycle.

If no DLT in first 3 participants or 1 DLT in 6 participants in Cohort 2B, then enrollment into Cohort 3B.

其他名称：
  • LY3012215
生物：IMC-20D7S (Cohort 3B)

30 mg/kg i.v. every 3 weeks.

Administered every 3 weeks on Days 1 and 22 of each treatment cycle.

其他名称：
  • LY3012215

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Maximum Tolerated Dose (MTD) of IMC-20D7S
大体时间：Baseline to toxicity [up to end of Cycle 1 (4 or 6-week cycles)]
The MTD was defined as the dose preceding the dose level at which 2 participants experienced a dose-limiting toxicity (DLT) during treatment Cycle 1. A DLT was defined as any Grade 3 or above toxicity that emerged during study treatment and was clearly not attributable to malignant melanoma or co-medication and was possibly, probably, or definitely related to IMC-20D7S in the judgment of the investigator. No DLT was observed in the study; a provisional MTD was established.
Baseline to toxicity [up to end of Cycle 1 (4 or 6-week cycles)]
Number of Participants With Serious Adverse Events (SAEs), Other Non-Serious Adverse Events (AEs), or Death
大体时间：Baseline through 30 days post last dose (up to 31 weeks)
A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
Baseline through 30 days post last dose (up to 31 weeks)

次要结果测量

结果测量
措施说明
大体时间
IMC-20D7S Pharmacokinetics (PK): Maximum Concentration (Cmax)
大体时间：Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 hours (h) post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 hours (h) post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
IMC-20D7S PK: Minimal Concentration (Cmin)
大体时间：Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
IMC-20D7S PK: Half-life (t½)
大体时间：Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
IMC-20D7S PK: Clearance (Cl)
大体时间：Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
IMC-20D7S PK: Area Under the Concentration Versus Time Curve (AUC)
大体时间：Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
IMC-20D7S PK: Volume of Distribution (Vd) at Steady State
大体时间：Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
Number of Participants Who Develop Antibodies Against IMC-20D7S (Immunogenicity)
大体时间：Prior to the first and second infusion in each cycle up to Cycle 7 (4- and 6-week cycles)
Planned analyses for immunogenicity were not completed. A decision was made not to develop a validated immunogenicity assay because of the exploratory nature of the study and the analyses.
Prior to the first and second infusion in each cycle up to Cycle 7 (4- and 6-week cycles)
Progression-Free Survival (PFS)
大体时间：First dose to disease progression or death (up to 27 weeks)
PFS was determined for participants who went beyond their first disease assessment and completed at least 1 treatment beyond Week 1 of treatment Cycle 3.
First dose to disease progression or death (up to 27 weeks)
Recommend Doses for Phase 2/3 Studies Based on MTD
大体时间：Baseline to toxicity [up to end of Cycle 1 (4-or 6-week cycles)]
It was decided for administrative reasons to discontinue dosing at the provisional MTD rather than progress to Phase 1b.
Baseline to toxicity [up to end of Cycle 1 (4-or 6-week cycles)]

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Eli Lilly and Company

调查人员

  • 研究主任：E-mail: ClinicalTrials@ ImClone.com、Eli Lilly and Company

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2010年6月1日

初级完成 (实际的)

2012年8月1日

研究完成 (实际的)

2012年8月1日

研究注册日期

首次提交

2010年6月2日

首先提交符合 QC 标准的

2010年6月3日

首次发布 (估计)

2010年6月4日

研究记录更新

最后更新发布 (实际的)

2019年6月17日

上次提交的符合 QC 标准的更新

2019年3月11日

最后验证

2019年3月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • 13945
  • CP22-0901 (其他标识符：ImClone, LLC)
  • I4Z-IE-JDEA (其他标识符：Eli Lilly and Company)

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