An Open-Label Phase 1a/1b Dose-Escalation and Expansion Study Investigating the Safety, Pharmacokinetics, Pharmacodynamics, and Activity of AB248 Alone or in Combination With Pembrolizumab in Adult Patients With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 552
- 试验地点
- 20
- 主要终点
- Frequency of Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
This is a phase I, First-in-Human (FIH), open-label study to evaluate the safety, tolerability, pharmacokinetic (PK) profile, and preliminary efficacy of AB248 as monotherapy OR in combination with pembrolizumab in adult participants with locally advanced or metastatic solid tumors. The study will consist of a dose escalation and a dose expansion stage.
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
- •Age ≥18 years of age at the time consent is signed.
- •Has adequate end organ function per laboratory testing.
- •Pregnancy prevention requirements
- •Has measurable disease per RECIST 1.1 as assessed by the local site Investigator/radiology.
- •Has a performance status of 0 or 1 on Eastern Cooperative Oncology Group scale.
- •Histologic documentation of incurable, locally advanced or metastatic tumor of the type being evaluated in individual cohorts
排除标准
- •Has a diagnosis of immunodeficiency.
- •Has a history of a previous, additional malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 5 years.
- •Has known active CNS metastases and/or carcinomatous meningitis.
- •Has an active autoimmune disease that has required systemic treatment in the past 2 years.
- •Has an active infection requiring systemic therapy.
- •Inability to comply with study and follow-up procedures.
- •Has had a severe hypersensitivity reaction (Grade ≥3) to treatment with pembrolizumab, another monoclonal antibody, or has history of any hypersensitivity to any components of the study treatments or any of their excipients.
- •Has received prior systemic anticancer therapy including investigational agents within 4 weeks (or, if shorter, within 5 half-lives for kinase inhibitors) prior to first dose of study treatment.
- •Has received prior radiotherapy within 2 weeks of start of study treatment or has had a history of radiation pneumonitis.
- •Receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment.
- •Has received previous treatment with another agent targeting the IL-2, IL-7, or IL-15 receptors.
- •Is expected to require any other form of antineoplastic therapy while on study
研究组 & 干预措施
etakafusp alfa (AB248) Monotherapy Indication Expansion
etakafusp alfa (AB248) will be administered intravenously as a single agent in disease specific cohorts
干预措施: etakafusp alfa (AB248) (Biological)
etakafusp alfa (AB248) + pembrolizumab Combination Indication Expansion
etakafusp alfa (AB248) and pembrolizumab will be administered intravenously in disease specific cohorts
干预措施: etakafusp alfa (AB248) (Biological)
etakafusp alfa (AB248) Monotherapy Dose-Escalation
etakafusp alfa (AB248) will be administered intravenously as a single agent
干预措施: etakafusp alfa (AB248) (Biological)
etakafusp alfa (AB248) + pembrolizumab Combination Dose-Escalation
etakafusp alfa (AB248) and pembrolizumab will be administered intravenously
干预措施: etakafusp alfa (AB248) (Biological)
etakafusp alfa (AB248) + pembrolizumab Combination Dose-Escalation
etakafusp alfa (AB248) and pembrolizumab will be administered intravenously
干预措施: pembrolizumab (Biological)
etakafusp alfa (AB248) + pembrolizumab Combination Indication Expansion
etakafusp alfa (AB248) and pembrolizumab will be administered intravenously in disease specific cohorts
干预措施: pembrolizumab (Biological)
结局指标
主要结局
Frequency of Dose-Limiting Toxicities (DLTs)
时间窗: From Study Day 1 through up to Day 21, Day 28, or Day 42
Based on toxicities observed
Frequency of Serious Adverse Events (SAEs)
时间窗: Signed consent up to 90 days after discontinuing study treatment
Based on toxicities observed
Frequency of Adverse Events of Special Interest (AESIs)
时间窗: Study Day 1 up to 90 days after discontinuing study treatment
Based on toxicities observed
Frequency of Adverse Events (AEs) leading to dose interruption or treatment discontinuation and death
时间窗: Signed consent up to 90 days after discontinuing study treatment
Based on toxicities observed
Frequency of Treatment Emergent Adverse Events (TEAEs)
时间窗: Study Day 1 up to 90 days after discontinuing study treatment
Based on toxicities observed
次要结局
- Duration of Response (DOR) according to RECIST version 1.1(Study Day 1 up to approximately 24 months)
- Disease Control Rate (DCR) according to RECIST version 1.1(Study Day 1 up to approximately 24 months)
- Objective Response Rate (ORR) according to RECIST version 1.1(Study Day 1 up to approximately 24 months)
- Progression-Free Survival (PFS) according to RECIST version 1.1(Study Day 1 until the date of first documented progression or date of death from any cause, assessed up to approximately 24 months)
- Maximum observed blood concentration (Cmax) of AB248(Study Day 1 up to approximately 24 months)
- Frequency of anti-drug antibodies (ADA)s to AB248(Study Day 1 up to approximately 24 months)
- Changes in CD8+ T cell density in tumor tissues(Study Day 1 to approximately 1 month)
- AUC Area under the Plasma Concentration versus Time Curve (AUC) of AB248(Study Day 1 up to approximately 24 months)
- Overall Survival (OS) according to RECIST version 1.1(Study Day 1 up to time of death, assessed up to approximately 24 months)
- Elimination half-life (t1/2) of AB248(Study Day 1 up to approximately 24 months)
- Quantification of peripheral blood CD8+ T cell pharmacodynamics(Study Day 1 up to approximately 24 months)