A Phase I/II, Open-label, Multicenter Study of ALE.P03 (Claudin-1 Targeted Antibody-drug Conjugate) as a Monotherapy in Adult Patients With Selected Advanced or Metastatic CLDN1+ Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 180
- 试验地点
- 47
- 主要终点
- Number of Patients with Dose Limiting Toxicities (DLTs) (Phase I)
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.P03 monotherapy in adult patients with selected squamous solid tumors.
详细描述
This Study has a Phase I ALE.P03 monotherapy dose escalation and recommended dose for expansion (RDE) study and a Phase II study of ALE.P03 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
- 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
- •Have histologically and cytologically metastatic confirmed advanced or metastatic colorectal cancer, intrahepatic cholangiocarcinoma, squamous non-small cell lung cancer, urothelial carcinoma, and cervical squamous cell carcinoma.
- •Have documented radiological disease progression at study entry.
- •Have provided tissue for CLDN1 (Claudin-1) analysis in a central laboratory.
- •Phase I Dose Escalation:
- •- Received and being refractory/intolerant to available systemic standard of care (SOC) regimens (based on local institutional guidelines) for advanced disease.
- •Phase I RDE and Phase II:
- •Received 1-2 available systemic SOC regimens (based on local institutional guidelines) for advanced disease and being refractory or intolerant to treatment.
- •Patients with actionable oncogenic drivers: received feasible targeted therapy.
- •Applicable for Phase I Dose Escalation, Phase I RDE and Phase II:
- •Measurable disease per RECIST 1.1, as determined by the site.
- •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Groups Performance Status.
- •Demonstrate adequate bone marrow and organ function as per the protocol.
排除标准
- •SqNSCLC and CSCC: diagnosed with a tumor of predominantly non-squamous histology result or adenocarcinoma.
- •Has received antineoplastic therapies prior to study intervention within specified time frame.
- •Has rapidly progressing disease.
- •Has known active central nervous system metastases and/or carcinomatous meningitis.
- •Has a history of (non-infectious) interstitial lung disease/pneumonitis that required steroids or current symptomatic or clinically significant pneumonitis requiring steroids and/or immunosuppressive therapies.
- •Has clinically significant gastrointestinal bleeding.
- •Has an active infection requiring systemic treatment.
- •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the clinical study.
研究组 & 干预措施
Phase I Dose Escalation- ALE.P03
Patients will receive ALE.P03 as monotherapy via intravenous infusion. The ALE.P03 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.P03 (Drug)
Phase II- ALE.P03
Patients will receive ALE.P03 as monotherapy via intravenous infusion at the RP2D, or according to the dosing schedule after the dose expansion phase.
干预措施: ALE.P03 (Drug)
Phase I Dose Expansion- ALE.P03
Patients will receive ALE.P03 as monotherapy via intravenous infusion. The safe recommended doses of ALE.P03 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.P03 (Drug)
结局指标
主要结局
Number of Patients with Dose Limiting Toxicities (DLTs) (Phase I)
时间窗: Up to 28 days
DLTs as defined in the protocol will be assessed to evaluate safety and tolerability of ALE.P03 (Phase I Dose Escalation), and to establish RP2D for ALE.P03 (Phase I RDE).
Number of Patients with Adverse Events (Phase I)
时间窗: From Day 1 up to Safety follow-up (30 ± 5 days post last dose [Up to 4 years])
Adverse events will be assessed to evaluate safety and tolerability of ALE.P03 (Phase I Dose Escalation), and to establish RP2D for ALE.P03 (Phase I RDE).
Overall Response Rate (ORR) (Phase I)
时间窗: From ALE.P03 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 4 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.P03 (Phase I RDE)
Duration of Response (DoR) (Phase I)
时间窗: From ALE.P03 treatment initiation until disease progression or study completion (Up to 4 years)
The DoR is defined for patients achieving a CR or PR as per Investigator review according to RECIST 1.1 to disease progression before new anti-cancer therapy or death of any cause, whichever occurs earlier. This is assessed to establish RP2D for ALE.P03 (Phase I RDE).
Overall Response Rate (ORR) (Phase II)
时间窗: From ALE.P03 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 4 years)
The ORR is assessed to assess anti-tumor activity of ALE.P03 (Phase II).
Duration of Response (DoR) (Phase II)
时间窗: From ALE.P03 treatment initiation until disease progression or study completion (Up to 4 years)
The DoR is defined for patients achieving a confirmed CR or PR as the time from the initial response of CR or PR to disease progression before new anti-cancer therapy or death of any cause, whichever occurs earlier. This is assessed to assess anti-tumor activity of ALE.P03 (Phase II).
Number of Patients with Dose Limiting Toxicities (DLTs) (Phase I)
时间窗: Up to 28 days
DLTs as defined in the protocol will be assessed to evaluate safety and tolerability of ALE.P03 (Phase I Dose Escalation), and to establish RP2D for ALE.P03 (Phase I RDE).
Number of Patients with Adverse Events (Phase I)
时间窗: From Day 1 up to Safety follow-up (30 ± 5 days post last dose [Up to 4 years])
Adverse events will be assessed to evaluate safety and tolerability of ALE.P03 (Phase I Dose Escalation), and to establish RP2D for ALE.P03 (Phase I RDE).
Overall Response Rate (ORR) (Phase I)
时间窗: From ALE.P03 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 4 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.P03 (Phase I RDE)
Duration of Response (DoR) (Phase I)
时间窗: From ALE.P03 treatment initiation until disease progression or study completion (Up to 4 years)
The DoR is defined for patients achieving a CR or PR as per Investigator review according to RECIST 1.1 to disease progression before new anti-cancer therapy or death of any cause, whichever occurs earlier. This is assessed to establish RP2D for ALE.P03 (Phase I RDE).
Overall Response Rate (ORR) (Phase II)
时间窗: From ALE.P03 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 4 years)
The ORR is assessed to assess anti-tumor activity of ALE.P03 (Phase II).
Duration of Response (DoR) (Phase II)
时间窗: From ALE.P03 treatment initiation until disease progression or study completion (Up to 4 years)
The DoR is defined for patients achieving a confirmed CR or PR as the time from the initial response of CR or PR to disease progression before new anti-cancer therapy or death of any cause, whichever occurs earlier. This is assessed to assess anti-tumor activity of ALE.P03 (Phase II).
次要结局
- Area under the concentration-time curve over the dosing interval (AUCtau) (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 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)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Area under the concentration-time curve from pre-dose (time 0) extrapolated to infinite time (AUCinf) (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Maximum Concentration (Cmax) (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Minimum concentration (Cmin) (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Concentration at the end of a dosing interval (Ctrough) (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- The terminal elimination rate constant (KeL) (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Terminal elimination half-life (t½) (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Time of Maximum Concentration (tmax) (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Average Concentration (Cavg) (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Number of Patients with Presence of anti-ALE.P03 Antibodies (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Number of Patients with Positive anti-ALE.P03 Antibodies (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Number of Patients with Adverse Events (Phase I RDE and Phase II)(From Day 1 up to Safety follow-up (30 ± 5 days post last dose [Up to 4 years])
- Disease control rate (DCR) (Phase I and II)(From ALE.P03 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 4 years))
- Median Progression-Free Survival (PFS) rate at 6 and 12 Months (Phase I and II)(At 6 and 12 months after initiation of ALE.P03 treatment)
- Median Overall Survival (OS) rate at 6, 12, and 24 Months (Phase I and II)(At 6, 12, and 24 months after initiation of ALE.P03 treatment)
- Blood Concentration of ALE.P03 Antibody-drug Conjugate (ADC) (Phase I and II)(Phase I and II: From Day 1 until at end of treatment visit (EoT) (Up to 4 years))
- Blood Concentrations of Total Antibody (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Blood Concentrations of Payload (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Number of Patients with Adverse Events (Phase I RDE and Phase II)(From Day 1 up to Safety follow-up (30 ± 5 days post last dose [Up to 4 years])
- Disease control rate (DCR) (Phase I and II)(From ALE.P03 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 4 years))
- Median Progression-Free Survival (PFS) rate at 6 and 12 Months (Phase I and II)(At 6 and 12 months after initiation of ALE.P03 treatment)
- Median Overall Survival (OS) rate at 6, 12, and 24 Months (Phase I and II)(At 6, 12, and 24 months after initiation of ALE.P03 treatment)
- Blood Concentration of ALE.P03 Antibody-drug Conjugate (ADC) (Phase I and II)(Phase I and II: From Day 1 until at end of treatment visit (EoT) (Up to 4 years))
- Blood Concentrations of Total Antibody (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Blood Concentrations of Payload (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Area under the concentration-time curve over the dosing interval (AUCtau) (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 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)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Area under the concentration-time curve from pre-dose (time 0) extrapolated to infinite time (AUCinf) (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Maximum Concentration (Cmax) (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Minimum concentration (Cmin) (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Concentration at the end of a dosing interval (Ctrough) (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- The terminal elimination rate constant (KeL) (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Terminal elimination half-life (t½) (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Time of Maximum Concentration (tmax) (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Average Concentration (Cavg) (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Number of Patients with Presence of anti-ALE.P03 Antibodies (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))
- Number of Patients with Positive anti-ALE.P03 Antibodies (Phase I and II)(Phase I and II: From Day 1 until at EoT (Up to 4 years))