GUARDIAN-101: A Phase 1 Dose Escalation and Expansion Study of CLSP-1025 in Adult Patients With Solid Tumors That Harbor the p53 R175H Mutation
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 90
- 试验地点
- 30
- 主要终点
- Part A: Determine the maximum tolerated dose (MTD) and/or the recommended dose(s) for expansion (RDE[s])
研究概览
简要总结
Phase 1 dose escalation and expansion study of CLSP-1025, a first-in-class HLA-A*02:01 specific T cell engager (TCE) targeting solid tumors that harbor the p53 R175H mutation.
详细描述
This Phase 1, open-label, multicenter study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of CLSP-1025 when administered to HLA-A*02:01-positive adult patients with advanced solid tumors that harbor the p53 R175H mutation. The study will be conducted in 2 parts: Part A Monotherapy Dose Escalation to determine the recommended dose(s) for expansion (RDE[s]) and Part B Monotherapy Expansion to explore the preliminary antitumor activity as well as further characterize the safety, tolerability, PK, and PD of CLSP-1025 at the RDE(s).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be at least 18 years of age at the time of signing the informed consent.
- •Patients must be willing and able to provide written informed consent
- •Patients must have locally advanced or metastatic solid tumors that have progressed after standard of care therapy or for which no standard therapy exists
- •Tumors must harbor a TP53 R175H variant mutation confirmed by an accredited laboratory-based test
- •Patients must be HLA-A*02:01 positive by central assay
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at the time of enrollment
- •Adequate hematological, renal and hepatic function
- •Per Investigator judgement, patient is willing and able to complete study visits and/or procedures per the protocol and comply with study requirements for study participation
排除标准
- •Patients with Li-Fraumeni syndrome or other known germline p53 R175H mutation
- •Patients who have received other p53 R175H-directed therapies
- •Patients who have not fully recovered from adverse events due to previous anticancer therapies
- •Patients with active infection requiring systemic antimicrobial therapy
- •Any other primary malignancy within the 2 years prior to enrollment (except for non- melanoma skin cancer, carcinoma in situ (eg, cervix, bladder, breast) or prostate cancer in remission.
- •Known active central nervous system metastases and/or carcinomatous meningitis
研究组 & 干预措施
Part A: Monotherapy Dose Escalation of CLSP-1025
Dose escalation of CLSP-1025 in HLA-A*02:01-positive adult patients with advanced solid tumors that harbor the p53 R175H mutation
干预措施: CLSP-1025 (Drug)
Part B: Monotherapy Dose Expansion of CLSP-1025
Dose expansion of CLSP-1025 in HLA-A*02:01-positive adult patients with advanced solid tumors that harbor the p53 R175H mutation
干预措施: CLSP-1025 (Drug)
结局指标
主要结局
Part A: Determine the maximum tolerated dose (MTD) and/or the recommended dose(s) for expansion (RDE[s])
时间窗: 28 days after infusion
Rate of dose-limiting toxicities (DLTs) after infusion of CLSP-1025
Part B: Evaluate the Objective response rate (ORR) of CLSP-1025 as a monotherapy in HLA-selected patients with advanced solid tumors that express the p53 R175H mutation
时间窗: Up to 24 months after infusion
Objective response rate (ORR) per RECIST V1.1 determined by Investigator assessment
次要结局
- Time of Treatment(Up to 24 months after infusion)
- Overall Survival (OS)(Up to 24 months after infusion)
- Number of patients with treatment-emergent adverse events, as assessed by CTCAE, v5.0(Up to 24 months after infusion)
- Number of patients with treatment-related adverse events, as assessed by CTCAE, v5.0(Up to 24 months after infusion)
- Number of patients with clinically significant changes in QTcF Interval(Up to 24 months after infusion)
- Maximum plasma concentration (Cmax) of CLSP-1025(Pre-dose and up to 168 hours post-dose)
- Minimum plasma concentration (Cmin) of CLSP-1025(Pre-dose and up to 168 hours post-dose)
- Area under the curve at the end of the dosing interval (AUCtau) of CLSP-1025(Pre-dose and up to 168 hours post-dose)
- Half-life (t1/2) of CLSP-1025(Pre-dose and up to 168 hours post-dose)
- Assess the immunogenicity of CLSP-1025(Up to 24 months after infusion)
- Part A: Objective Response Rate (ORR)(Up to 24 months after infusion)
- Duration of response (DOR)(Up to 24 months after infusion)
- Time to Response(Up to 24 months after infusion)
- Disease Control Rate(Up to 24 months after infusion)
- Progression-free survival (PFS)(Up to 24 months after infusion)