A First-in-human Dose-escalation and Expansion Study With the Antibody-drug Conjugate SYD1875 to Evaluate the Safety, Pharmacokinetics and Efficacy in Patients With 5T4-expressing Locally Advanced or Metastatic Solid Tumours
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Byondis B.V.
- 入组人数
- 31
- 试验地点
- 3
- 主要终点
- Incidence of dose-limiting toxicities
研究概览
简要总结
This is the first-in-human study with SYD1875, an antibody-drug conjugate (ADC) comprising of a humanized IgG1 monoclonal antibody directed against the 5T4 oncofetal antigen covalently conjugated to a duocarmycin-based linker-drug. This study includes a dose-escalation part (Part 1) in which the maximum tolerated dose (MTD) and recommended dose for expansion (RDE) will be determined, and an expansion part (Part 2) to evaluate efficacy and safety in specific patient cohorts.
详细描述
Cancer cells can have different kinds of proteins on their cell surface; one of these is the oncofetal antigen 5T4. 5T4 plays an important role in the development of cancer. Currently no drugs are available that work via the 5T4 antigen.
The new cancer drug SYD1875 is being developed by Byondis B.V. SYD1875 is an antibody-drug conjugate and consists of two parts: an antibody and a linker-drug moiety containing a toxin. The antibody part binds to 5T4 on the surface of the cancer cell. When SYD1875 binds to this cancer cell, it will be internalized by the cell. After proteolytic cleavage of the linker, the toxin will be split off in the cell and the cancer cell will be killed. Thus, SYD1875 can be considered as a form of targeted chemotherapy.
This is the first study in which SYD1875 is administered to humans. The study consists of two parts:
Part 1 is the dose-escalation part in which a low dose of SYD1875 is given to cancer patients. If it is well tolerated, a higher dose of SYD1875 will be given to other cancer patients until the maximum tolerated dose is reached.
In Part 2 of the study, groups of patients with a specific type of cancer will receive the SYD1875 dose which has been selected for further evaluation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Patient with histologically-confirmed, locally advanced or metastatic cancer who has progressed on standard therapy or for whom no standard therapy exists, with the following restriction:
- •Part 1: solid tumours of any origin
- •Part 2: three patient cohorts
- •Tumour 5T4 membrane staining according protocol
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1;
- •Adequate organ function
- •For Part 2: measurable disease
排除标准
- •Having been treated with:
- •5T4-targeting therapy at any time
- •Trastuzumab duocarmazine (SYD985) at any time
- •Other anticancer therapy within 4 weeks or as defined in the protocol
- •Hormone therapy within 1 week
- •History or presence of keratitis, clinically significant renal disease, lung disease, or cardiovascular disease as specified in the protocol
- •Symptomatic brain metastases, brain metastases requiring steroids or treatment for brain metastases within 8 weeks
研究组 & 干预措施
SYD1875
5T4-targeting Antibody-Drug Conjugate
干预措施: SYD1875 (Drug)
结局指标
主要结局
Incidence of dose-limiting toxicities
时间窗: 21 days
Part 1
次要结局
- Objective response rate(21 days)