A Phase I/II, Open-Label, Multicenter Study of ALE.P02 (Claudin-1 Targeted Antibody-Drug Conjugate) as a Monotherapy in Adult Patients With Selected Advanced or Metastatic CLDN1+Squamous Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 170
- 试验地点
- 52
- 主要终点
- Number of Patients with Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic, preliminary anti-tumor activity, and to determine the recommended Phase II dose (RP2D) of the ALE.P02 monotherapy in adult patients with selected squamous solid tumors.
详细描述
This Study has a Phase I ALE.P02 monotherapy dose escalation and recommended dose for expansion (RDE) study and a Phase II study of ALE.P02 as monotherapy at RP2D in adult patients with selected advanced or metastatic Claudin-1 positive (CLDN1+) cancers.
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
- •Have disease and treatment history as: Have histologically or cytologically confirmed advanced locally recurrent and inoperable or metastatic SqNSCLC, HNSCC (nasopharyngeal cancer included), ESCC or CSCC.
- •Phase I Dose Escalation: Have received at least one systemic standard of care regimen and being refractory or intolerant to the treatment.
- •Phase I RDE and Phase II: Have received no more than 2 lines of systemic standard of care regimen and being refractory or intolerant to the treatment.
- •Have provided tissue for CLDN1 analysis in a central laboratory.
- •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group Performance Scale.
- •Demonstrate adequate bone marrow and organ function.
- •Patients must have recovered from all toxicities led by prior treatment.
- •Have measurable disease based on RECIST 1.1 as determined by the site.
排除标准
- •Diagnosed with cancers of predominantly non-squamous histology (eg, adenosquamous carcinoma) or adenocarcinoma.
- •Has received antineoplastic therapies prior to study intervention within specified time frame.
- •Has rapidly progressing disease (eg, tumor bleeding, uncontrolled tumor pain).
- •Patients with uncontrolled diabetes.
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Has clinically significant gastrointestinal bleeding and has an active infection requiring systemic treatment and has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the clinical study, interfere with the patient's participation for the full duration of the clinical study, or is not in the best interest of the patient to participate.
- •Concomitant use of drugs that are known to prolong or shorten QT and/or have known risk of Torsades de Pointes.
研究组 & 干预措施
Phase II- ALE.P02
Patients will receive ALE.P02 as monotherapy via intravenous infusion at the RP2D, or according to the dosing schedule after the dose expansion phase.
干预措施: ALE.P02 (Drug)
Phase I Dose Expansion- ALE.P02
Patients will receive ALE.P02 as monotherapy via intravenous infusion. The safe recommended dose of ALE.P02 will be given in Phase I dose expansion part of the study to identify Recommended Phase II Dose (RP2D) for Phase II.
干预措施: ALE.P02 (Drug)
Phase I Dose Escalation- ALE.P02
Patients will receive ALE.P02 as monotherapy via intravenous infusion. The ALE.P02 will be given at an escalated dose until Maximum tolerated dose (MTD) and/or a safe recommended Dose for Expansion (RDE) is determined in Phase I dose escalation part of the study.
干预措施: ALE.P02 (Drug)
结局指标
主要结局
Number of Patients with Dose Limiting Toxicities (DLTs)
时间窗: Up to 28 days
DLTs as defines in the protocol will be assessed to evaluate safety and tolerability of ALE.P02 (Phase I Dose Escalation), and to establish RP2D for ALE.P02 (Phase I RDE).
Number of Patients with Adverse Events
时间窗: Screening (day -28 to day -1) up to Safety follow-up (30 ± 5 days post last dose [Up to 3.5 years])
Adverse events will be assessed to evaluate safety and tolerability of ALE.P02 (Phase I Dose Escalation), and to establish RP2D for ALE.P02 (Phase I RDE).
Overall Response Rate (ORR) (Phase I)
时间窗: From ALE.P02 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 3.5 years)
The ORR is the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1.) This is assessed to establish RP2D for ALE.P02 (Phase I RDE)
Duration of Response (DoR) (Phase I)
时间窗: From ALE.P02 treatment initiation until disease progression or study completion (Up to 3.5 years)
The DoR is defined for patients achieving a confirmed CR or PR as the time from the initial response of CR or PR per Investigator review according to RECIST 1.1 to disease progression or death of any cause, whichever occurs earlier. This is assessed to establish RP2D for ALE.P02 (Phase I RDE).
Overall Response Rate (ORR) (Phase II)
时间窗: From ALE.P02 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 3.5 years)
The ORR is assessed to assess anti-tumor activity of ALE.P02 (Phase II).
Duration of Response (DoR) (Phase II)
时间窗: From ALE.P02 treatment initiation until disease progression or study completion (Up to 3.5 years)
The DoR is assessed to assess anti-tumor activity of ALE.P02 (Phase II).
次要结局
- Disease control rate (DCR) (Phase I and II)(From ALE.P02 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 3.5 years))
- Median Progression-Free Survival (PFS) at 6 and 12 Months (Phase I and II)(At 6 and 12 months after initiation of ALE.P02 treatment)
- Median Overall Survival (OS) at 6, 12, and 24 Months (Phase I and II)(At 6, 12, and 24 months after initiation of ALE.P02 treatment)
- Blood Concentration of ALE.P02 Antibody-drug Conjugate (ADC)(Phase I and II: Cycle 1 Day 1 until at end of treatment visit (EoT) (Up to 3.5 years))
- Blood Concentration of Total Antibody(Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years))
- Blood Concentrations of Payload(Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years))
- Area under the concentration-time curve over the dosing interval (AUCtau)(Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years))
- Area under the concentration-time curve from pre-dose (time 0) to the time of the last quantifiable concentration (AUClast)(Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years))
- Area under the concentration-time curve from pre-dose (time 0) extrapolated to infinite time (AUCinf)(Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years))
- Maximum Concentration (Cmax)(Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years))
- Minimum concentration (Cmin)(Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years))
- Concentration at the end of a Dosing Interval (Ctrough)(Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years))
- The terminal elimination rate constant (KeL)(Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years))
- Terminal elimination half-life (t½)(Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years))
- Time of Maximum Concentration (tmax)(Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years))
- Average Concentration (Cavg)(Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years))
- Number of Patients with Presence of anti-ALE.P02 Antibodies(Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years))