A PHASE 1/1b MULTICENTER STUDY TO EVALUATE THE HUMANIZED ANTI-CD73 ANTIBODY, CPI-006, AS A SINGLE AGENT OR IN COMBINATION WITH CIFORADENANT, WITH PEMBROLIZUMAB, AND WITH CIFORADENANT PLUS PEMBROLIZUMAB IN ADULT SUBJECTS WITH ADVANCED CANCERS
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 117
- 试验地点
- 27
- 主要终点
- Incidence of dose-limiting toxicities (DLTs) of CPI-006 as a single agent and in combination with ciforadenant and with pembrolizumab.
研究概览
简要总结
This is a Phase 1/1b open-label, dose escalation and dose expansion study of CPI-006, a humanized monoclonal antibody (mAb) targeting the CD73 cell-surface ectonucleotidase in adult subjects with select advanced cancers. CPI-006 will be evaluated as a single agent, in combination with ciforadenant (an oral adenosine 2A receptor antagonist), in combination with pembrolizumab (an anti-PD1 antibody), and in combination with ciforadenant and pembrolizumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0-
- •Documented incurable cancer with one of the following histologies: nonsmall cell lung cancer, renal cell cancer, triple negative breast cancer, colorectal cancer with microsatellite instability(MSI), bladder cancer, cervical cancer, uterine cancer, sarcoma, endometrial cancer, and metastatic castration resistant prostate cancer.
- •At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
- •For Escalation: At least 1 but not more than 5 prior systemic therapies for advanced/ recurrent or progressing disease. For Expansion: Subject must have progressed on, be refractory to, or intolerant to 1-3 prior systemic therapies.
- •Willingness to provide tumor biopsies.
- •Exclusion Criteria
- •History of severe hypersensitivity reaction to monoclonal antibodies.
- •Subjects who have received prior therapy with regimens containing cytotoxicT-lymphocyte antigen-4 (CTLA-4), programmed cell death ligand 1 (PDL1), or PD1 antagonists are NOT permitted to enroll unless all adverse events (AEs) while receiving prior immunotherapy have resolved to Grade 1 or baseline prior to screening.
- •History of (non-infectious) pneumonitis that required steroids or subject has current pneumonitis.
- •The use of any investigational medication or device in the 30 days prior to screening and throughout the study is prohibited.
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
排除标准
- 未提供
研究组 & 干预措施
Cohort 1a
CPI-006
干预措施: CPI-006 (Drug)
Cohort 2a
CPI-006
干预措施: CPI-006 (Drug)
Cohort1b
CPI-006 + ciforadenant
干预措施: CPI-006 + ciforadenant (Drug)
Cohort 1c
CPI-006 + pembrolizumab
干预措施: CPI-006 + pembrolizumab (Drug)
Cohort 2b
CPI-006 + ciforadenant
干预措施: CPI-006 + ciforadenant (Drug)
Cohort 2c
CPI-006 + pembrolizumab
干预措施: CPI-006 + pembrolizumab (Drug)
结局指标
主要结局
Incidence of dose-limiting toxicities (DLTs) of CPI-006 as a single agent and in combination with ciforadenant and with pembrolizumab.
时间窗: From start of treatment to end of treatment, up to 36 months
Incidence of treatment-emergent adverse events as assessed by NCI CTCAE v.4.03, of CPI-006 as single agent and in combination with ciforadenant and with pembrolizumab.
时间窗: From start of treatment to end of treatment, up to 36 months
Identify the MDL(maximum dose level) of single agent CPI-006
时间窗: From start of treatment to end of treatment, up to 36 months
次要结局
- Area under the curve (AUC) of CPI-006(Day 1, 2, 8 , and 15 of Cycle 1 & 4 (each cycle is 21 days).)
- Objective response rate per RECIST v.1.1 criteria of CPI-006 as single agent and in combination with ciforadenant and with pembrolizumab.(From start of treatment to end of treatment, up to 36 months)
- Maximum serum concentration (Cmax) of CPI-006(Day 1, 2, 8 , and 15 of Cycle 1 & 4 (each cycle is 21 days).)