Phase 1, First-in-Human Study to Assess the Safety, Tolerability and Anti-tumor Activity of CDR404 in HLA-A*02:01 Participants With MAGE-A4 Expressing Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- CDR-Life AG
- 入组人数
- 42
- 试验地点
- 17
- 主要终点
- Presence of dose limiting toxicities (DLTs)
研究概览
简要总结
CDR404 is a highly potent and specific T-cell engaging bispecific and bivalent antibody designed for the treatment of cancers positive for the tumor-associated antigen melanoma-associated antigen 4 (MAGE-A4). This is a first-in-human study designed to evaluate the safety, tolerability, and preliminary anti-tumor activity of CDR404 in adult patients who have the appropriate germline human leukocyte antigen HLA-A*02:01 tissue marker and whose cancer is positive for MAGE-A4.
详细描述
The CDR404-001 Phase 1 study will enrol patients with locally advanced, unresectable or metastatic tumors expressing MAGE-A4, which include advanced solid tumors, and will be conducted in multiple phases:
- To identify the maximum tolerated dose (MTD) and pharmacologically effective dose range (PEDR) for CDR404
- To assess preliminary evidence of anti-tumor activity of CDR404
- To characterise the pharmacokinetics of CDR404
- To characterise the immunogenicity of CDR404
- To assess translational biomarkers
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
- •Provision of written informed consent
- •HLA-A*02:01 positive
- •MAGE-A4 positive tumor
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) [ECOG PS] 0 or 1
- •Selected advanced solid tumors
- •Relapsed from, refractory to, or intolerant of standard therapy
- •Measurable disease per RECIST v1.1
- •Adequate organ function
- •If applicable, must agree to use highly effective contraception
排除标准
- •Symptomatic or untreated central nervous system metastasis
- •Inadequate washout from prior anticancer therapy
- •Significant ongoing toxicity from prior anticancer treatment
- •Recent surgery
- •Clinically significant cardiac disease
- •Active infection requiring systemic antibiotic treatment
- •Human immunodeficiency virus (HIV) at risk of acquired immunodeficiency syndrome (AIDS)-related outcomes
- •Active hepatitis B virus (HBV) or hepatitis C virus (HBC)
- •Ongoing treatment with systemic steroids or other immunosuppressive therapies
- •Significant secondary malignancy
- •History of chronic or recurrent active autoimmune disease requiring treatment
- •Uncontrolled intercurrent illness
- •Pregnancy or lactation.
研究组 & 干预措施
CDR404
Dose escalation
干预措施: CDR404 (Biological)
结局指标
主要结局
Presence of dose limiting toxicities (DLTs)
时间窗: From first dose to DLT period (21 days)
per Protocol
Anti-tumor response: Overall Response Rate (ORR)
时间窗: From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months
per RECIST 1.1
Incidence and severity of (serious) adverse events ([S]AEs)
时间窗: From first dose to 90 days after the last dose
AEs, SAEs
次要结局
- Disease control rate (DCR)(From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months)
- Progression-free Survival (PFS)(From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months)
- Serum drug levels of CDR404 at steady state (CL)(At the end of Cycle 1 and Cycle 2 (each cycle is 21 days))
- Area under the CDR404 serum concentration over time curve (AUC0-T)(At the end of Cycle 1 and Cycle 2 (each cycle is 21 days))
- Immunogenicity(From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months)
- Maximum serum concentration of CDR404 (Cmax)(At the end of Cycle 1 and Cycle 2 (each cycle is 21 days))
- Duration of response (DOR)(From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months)
- Trough serum concentration of CDR404 (Ctrough)(At the end of Cycle 1 and Cycle 2 (each cycle is 21 days))
- Time to maximum serum concentration of CDR404 (Tmax)(At the end of Cycle 1 and Cycle 2 (each cycle is 21 days))
- Overall Survival (OS)(From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months)
- Half-life of CDR404 (t1/2)(At the end of Cycle 1 and Cycle 2 (each cycle is 21 days))
- Volume of CDR404 distribution (Vd)(At the end of Cycle 1 and Cycle 2 (each cycle is 21 days))
- Average serum concentration of CDR404 (Cavg)(At the end of Cycle 1 and Cycle 2 (each cycle is 21 days))
- Accumulation ratio of CDR404 (Rac)(At the end of Cycle 1 and Cycle 2 (each cycle is 21 days))