A Phase 1 Study to Evaluate the Safety and Tolerability of MEDI4736 as Monotherapy or in Combination With Tremelimumab With or Without Azacitidine in Subjects With Myelodysplastic Syndrome After Treatment With Hypomethylating Agents
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 1
- 主要终点
- Subject's safety where no more than one out of six subjects experience DLTs at a given dose
研究概览
简要总结
This is a multicenter, open-label, Phase 1 study to assess the safety and antitumor activity of MEDI4736 as Monotherapy or in Combination with Tremelimumab with or without Azacitidine in Subjects with myelodysplastic syndrome after treatment with hypomethylating agents
详细描述
A dose-escalation and dose-expansion study of MEDI4736 (a monoclonal antibody that targets programmed cell death-1 ligand 1 [PD-L1]) to evaluate the safety, tolerability, PK, IM, and antitumor activity of MEDI4736 as monotherapy or in combination with Tremelimumab with or without Azacitidine in adult patients with myelodysplastic syndrome.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult male or female subjects with pathologically confirmed MDS who failed to respond, relapsed after an initial response, or were unable to tolerate hypomethylating agents, ECOG performance status of 0 - 2, and adequate organ and marrow function.
排除标准
- •Concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment, prior MAb against CTLA-4, PD-1, or PD-L1, alllogenic or haploidentical transplant, current immunosuppressive medication or autoimmune or inflammatory disease.
研究组 & 干预措施
MEDI4736 Evaluate MEDI4736 in MDS
Evaluate MEDI4736 monotherapy and MEDI4736 in combination with azacitidine after monotherapy progression in MDS
干预措施: MEDI4736 Evaluate MEDI4736 in MDS (Biological)
MEDI4736 Evaluate MEDI4736 in MDS
Evaluate MEDI4736 monotherapy and MEDI4736 in combination with azacitidine after monotherapy progression in MDS
干预措施: VIDAZA (Drug)
MEDI4736 + tremelimumab
Evaluate MEDI4736 in combination with tremelimumab
干预措施: tremelimumab (Biological)
MEDI4736 + tremelimumab + azacitidine
Evaluate MEDI4736 in combination with tremelimumab and azacitidine
干预措施: VIDAZA (Drug)
MEDI4736 + tremelimumab + azacitidine
Evaluate MEDI4736 in combination with tremelimumab and azacitidine
干预措施: tremelimumab (Biological)
结局指标
主要结局
Subject's safety where no more than one out of six subjects experience DLTs at a given dose
时间窗: 180 days
DLT (MEDI4736 monotherapy only) assessment will be done by reviewing adverse events (AEs), serious adverse events (SAEs), laboratory evaluations, vital signs, physical examinations, and electrocardiogram (ECG) results. For monotherapy or combo w/aza AEs, SAEs, lab evaluations, vital signs, physical exams, ECGs will be done.
Subject's safety overall (monotherapy and combination therapies)
时间窗: 730 days
Overall safety assessments will be done by reviewing adverse events (AEs, serious adverse events (SAEs), laboratory evaluations, vital signs, physical examinations and electrocardiogram (ECG) results.
次要结局
- Clinical outcome in terms of response: progression-free survival (PFS)(2 years)
- Clinical outcome in terms of response: survival (OS)(2 years)
- Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: area under the concentration-time curve(1 year)
- Clinical outcome in terms of response: duration of response(2 years)
- Clinical outcome in terms of response: transfusion requirements(2 years)
- Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: peak concentration(1 year)
- Health-related quality of life (QOL): health status (Part 1 only)(2 years)
- Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: clearance(1 year)
- Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: terminal half-life(1 year)
- Health-related quality of life (QOL): pain (Part 1 only)(2 years)
- Immunogenicity(1 year)
- Health-related quality of life (QOL): disease- and treatment-related symptoms (Part 1 only)(2 years)