A Phase 1 First Time in Human Study to Evaluate the Safety, Pharmacokinetics and Immunogenicity of MEDI5083 Alone or in Combination With Durvalumab, Tremelimumab, and/or Docetaxel in Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 9
- 主要终点
- Number of participants with Adverse Events (AEs) as a measure of safety
研究概览
简要总结
The purpose of this study is to evaluate the safety, pharmacokinetics and Immunogenicity of Medi5083 alone or in combination with Durvalumab,Tremelimumab, and/or Docetaxel in adult subjects with advanced solid tumors.
详细描述
This is a global Phase 1, first-time-in-human, multicenter, dose-escalation and dose-expansion study of MEDI5083 alone or in combination with Durvalumab, Tremelimumab, and/or Docetaxel.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 101 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years at the time of screening or age of consent according to local law
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Histologically or cytologically confirmed metastatic or recurrent tumor types
- •Subjects who have received prior immunotherapy may be eligible
- •Subjects must have at least one measurable lesion
- •Consent to provide archival tumor tissue and pre/on-treatment biopsies
- •Adequate organ and marrow function
- •Consent to use one highly effective method of contraception
排除标准
- •Receipt of any systemic anticancer therapy within 28 days prior to the first dose of MEDI5083
- •Concurrent enrollment in another clinical study
- •Active/prior autoimmune of inflammatory disorders
- •History of immunodeficiency, solid organ transplant, or tuberculosis
- •Known allergy/hypersensitivity to drug or components
- •Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression
- •Current or prior use of immunosuppressive medication within 14 days prior to the first dose of MEDI5083
结局指标
主要结局
Number of participants with Adverse Events (AEs) as a measure of safety
时间窗: From the time of consent through 120 days after last treatment
Safety Endpoint
Number of participants with Dose Limiting Toxicities (DLTs) as a measure of safety
时间窗: From the time of first dose through 28 days thereafter
Safety Endpoint
Antitumor activity endpoints OR, based on RECIST v1.1
时间窗: Part 3
Safety Endpoint
Number of participants with Serious Adverse Events (SAEs) as a measure of safety
时间窗: From the time of consent through 120 days after last treatment
Safety Endpoint
Discontinuation of investigational products due to toxicity
时间窗: From the time of first dose through end of study (2 years after last subject enrolled or earlier at sponsor discretion)
Safety Endpoint
The Maximum Tolerated Dose (MTD) or Highest Protocol-Defined Dose
时间窗: From the time of first dose through end of study (2 years after last subject enrolled or earlier at sponsor discretion)
Safety Endpoint
Clinically significant alterations in vital signs, laboratory parameters, physical examination, and electrocardiogram (ECG) results.
时间窗: From the time of first dose through end of study (2 years after last subject enrolled or earlier at sponsor discretion)
Safety Endpoint
次要结局
- Serum MEDI5083 concentration levels(From the time of first dose through 57 days after first treatment)
- Reduction in peripheral blood CD19+ B cells(From the time of first dose through 57 days after first treatment)
- Progression Free Survival (PFS) at 6 months (PFS-6)(From the time of first dose until 6 months after the last subject is dosed)
- Serum Durvalumab concentration levels collected over time(From the time of first dose through 29 days after first treatment)
- Serum tremelimumab concentration levels collected over time(From the time of first dose through 57 days after first treatment)
- Incidence of anti-drug antibody (ADA) responses to MEDI5083(From the time of first dose through 2 years after last treatment)
- Objective Response Rate (ORR)(From the time of consent through end of study (2 years after last subject enrolled or earlier at sponsor discretion))
- Overall Survival (OS)(From the time of consent through end of study (2 years after last subject enrolled or earlier at sponsor discretion))
- Disease Control Rate (DCR)(From the time of consent through end of study (2 years after last subject enrolled or earlier at sponsor discretion))
- Incidence of anti-drug antibody (ADA) responses to Durvalumab(From the time of first dose through 2 years after last treatment)
- Duration of Response (DoR)(From the time of consent through end of study (2 years after last subject enrolled or earlier at sponsor discretion))
- Incidence of anti-drug antibody (ADA) responses to tremelilumab(From the time of first dose through 2 years after last treatment)
- PD of MEDI5083 alone and in combination with Durvalumab and tremelimumab(From the time of first dose through 57 days after first treatment)
- Safety and tolerability of MEDI5083 with durvalumamb and docetaxel and in subjects with IO relapsed/refractory 2/3L NSCLC(From the time of first dose through 57 days after first treatment)