A First-in-human, Multicenter Dose Escalation and Multiple Cohort Expansion Phase 1a/b Study to Investigate Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ADCX-020 in Participants With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 290
- 试验地点
- 9
- 主要终点
- Ph1a: To determine the safety and tolerability of ADCX-020
研究概览
简要总结
The purpose of this first-in-human study is to explore the safety, pharmacokinetics and effects of the study drug ADCX-020 in patients with advanced and metastatic solid tumors. ADCX-020 is an investigational anticancer therapy called antibody drug conjugate.
This study is set up in multiple parts. In the first part of the study, participants receive increasing doses of ADCX-020. Then 2 or more doses will be assessed to identify the optimal dose. This optimal dose is subsequently evaluated for effect on different cancer types.
详细描述
This is a first-in-human (FIH) open-label, multicenter, dose escalation and multiple cohort expansion Phase 1a/b study to investigate safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of ADCX-020 monotherapy in participants with relapsed or refractory solid tumors, or who are intolerant to standard of care.
During dose escalation, Phase 1a, participants will receive escalating doses of ADCX-020 to identify the MTD based on the observation of DLTs. Intermediate and higher dose levels as well as alternative dosing regimens may be investigated during this part of the study.
Dose expansion, Phase 1b, will be initiated with a dose optimization of ADCX-020 using two or more dose levels of ADCX-020 and/or evaluating a different dosing regimen. Expansion in multiple cohorts is planned for selected patient populations using the RP2D.
Phase 1a will be overseen by a Dose Escalation Committee (DEC) and Phase 1b will be overseen by a Safety Review Committee (SRC).
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
- •Male and female participants ≥ 18 years of age
- •Ph1a: Locally advanced or metastatic solid tumor relapsed or PD following local standard treatments, for which no standard treatment is available
- •Ph1b: Eligible patients should have only received prior lines of systemic therapy according to SoC in the advanced/metastatic setting (not counting neoadjuvant/adjuvant treatment if completed >6 months prior to recurrence)
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Radiologically measurable disease by RECIST v1.1
- •Mandatory adequate tumor tissue sample available
- •Must have recovered from all clinically relevant toxicities from previous cancer therapies (to at least Grade 1, except for alopecia)
排除标准
- •Known allergies/hypersensitivity/intolerance to or contraindication to exatecan, or any excipient
- •Phase 1b: Prior antibody drug conjugate exposure with a topoisomerase 1 inhibitor payload
- •Uncontrolled or significant cardiac disease including left ventricular ejection fraction (LVEF) <50%, myocardial infarction or uncontrolled/unstable angina
- •Has clinically active central nervous system (CNS) metastases
- •Has a history of lung fibrosis or non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
- •Active corneal disease, or history of corneal disease within 12 months prior to enrollment
- •Other unacceptable abnormalities, medications or procedures as defined by protocol
研究组 & 干预措施
Phase 1a ADCX-020
Dose escalation of ADCX-020, intravenous
干预措施: ADCX-020 (Drug)
Phase 1b: ADCX-020
Dose optimization and expansion of ADCX-020, intravenous
干预措施: ADCX-020 (Drug)
结局指标
主要结局
Ph1a: To determine the safety and tolerability of ADCX-020
时间窗: Start of treatment until 30 days after last dose
Incidence and severity of treatment-emergent adverse events (TEAEs)
Ph1b: To determine the recommended Phase 2 dose (RP2D)
时间窗: Baseline to 30 days post last study drug administration
Cumulative incidence and severity of TEAEs, preliminary anti-tumor activity and pharmacokinetics and -dynamics findings
Ph1a: To determine the maximun tolerated dose (MTD) or recommended dose range for expansion and optimization
时间窗: Start of treatment to end of DLT observation period
Incidence of dose-limiting toxicities (DLTs) at different dose levels
Ph1b: To assess the objective response rate (ORR) of ADCX-020
时间窗: Baseline until the date of the first documented disease progression, death, or start of new anticancer therapy (approximately 24 months)
Preliminary efficacy based on ORR assessed by Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
次要结局
- Phase 1b: To evaluate overall survival (OS)(Baseline to approximately 24 months)
- To determine the terminal phase elimination half-life (t1/2) for ADCX-020(Start of treatment until 30 days after last dose)
- To assess prgression free survival (PFS)(Baseline until approximately 24 months)
- To determine the plasma concentration of ADCX-020(Start of treatment until 30 days after last dose)
- To determine the time to Cmax (Tmax) for ADCX-020(Start of treatment until 30 days after last dose)
- To determine the area under the plasma concentration-time curve (AUC) for ADCX-020(Start of treatment until 30 days after last dose)
- To evaluate duration of objective response (DoR)(Baseline until approximately 24 months)
- To evaluate the disease control rate (DCR)(Baseline until approximately 24 months)
- To evaluate the immunogenicity of ADCX-020(Start of treatment until 30 days after last dose)