NCT07403721招募中1 期
A Phase 1/1b Study Evaluating the Safety, Tolerability, and Pharmacokinetics of AMG 436 as Monotherapy and in Combination With Other Therapies in Participants With Microsatellite Instability-high (MSI-H)/Mismatch Repair Deficient (dMMR) Solid Tumors
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Amgen
- 入组人数
- 464
- 试验地点
- 26
- 主要终点
- Number of Participants with a Dose Limiting Toxicity (DLT)
研究概览
简要总结
The primary objectives of this trial are to evaluate the safety profile of AMG 436 and to determine the maximum tolerated dose (MTD) and/or the recommended dose for AMG 436 as monotherapy and in combination with other anti-cancer therapies in participants with MSI-H/dMMR solid tumors.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years).
- •Histologically confirmed MSI-H or dMMR metastatic or locally advanced solid tumor by local testing or central testing.
- •Tumor tissue (formalin-fixed, paraffin-embedded sample) archival block must be available. Participants without archived tumor tissue may enroll by undergoing tumor biopsy before dosing.
- •Disease measurable as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
- •Eastern Cooperative Oncology Group performance (ECOG) 0-
- •Adequate organ function as defined in the protocol.
排除标准
- •Participants with primary central nervous system (CNS) tumors.
- •Impaired cardiac function or clinically significant cardiac disease.
- •Major surgery within 28 days of trial day
- •Antitumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, hormonal therapy, or investigational agent) within 21 days of first dose of trial treatment, unless anti-tumor therapy is a therapy with 5 times the half-life being shorter than 21 days (in this case, enrollment may be allowed with washout from prior therapy of < 21 days.
- •Radiation therapy within 28 days of the first dose of trial treatment (or local or focal radiotherapy with palliative intent within 14 days of the first dose).
- •Gastrointestinal tract disease causing the inability to take per os (PO) medication, malabsorption syndrome, requirement for intravenous (IV) alimentation, uncontrolled inflammatory gastrointestinal disease (eg, Crohn's disease, ulcerative colitis).
研究组 & 干预措施
Part 2
Experimental
AMG 436 + combination dose escalation.
干预措施: AMG 436 (Drug)
Part 1A
Experimental
AMG 436 monotherapy dose escalation.
干预措施: AMG 436 (Drug)
Part 4
Experimental
AMG 436 + chemotherapy combination dose expansions.
干预措施: AMG 436 (Drug)
Part 1B: Food Effect Substudy
Experimental
Participants will receive AMG 436 under fasted and fed conditions (United States only).
干预措施: AMG 436 (Drug)
Part 3
Experimental
AMG 436 monotherapy Dose expansion and optimization.
干预措施: AMG 436 (Drug)
结局指标
主要结局
Number of Participants with a Dose Limiting Toxicity (DLT)
时间窗: Up to 21 days
Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: Up to 5 years
次要结局
- Maximum Serum Concentration (Cmax) of AMG 436(Up to 57 days)
- Minimum Serum Concentration (Cmin) of AMG 436(Up to 57 days)
- Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of AMG 436(Up to 57 days)
- Time to Achieve Cmax (Tmax) of AMG 436(Up to 57 days)
- Part 1B: Cmax of AMG 436 in the Fed and/or Fasted State(Up to 24 days)
- Part 1B: Tmax of AMG 436 in the Fed and/or Fasted State(Up to 24 days)
- Part 1B: AUC Over the Dosing Interval of AMG 436 in the Fed and/or Fasted State(Up to 24 days)
- Confirmed Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1(Up to 5 years)
- Duration of Response (DOR) per RECIST v1.1(Up to 5 years)
- Time to Response (TTR) per RECIST v1.1(Up to 5 years)
- Disease Control Rate (DCR) per RECIST v1.1(Up to 5 years)
- Progression-free Survival (PFS) per RECIST v1.1(Up to 5 years)
- Overall Survival (OS) per RECIST v1.1(Up to 5 years)
- Change From Baseline in Tumor Phosphorylated Checkpoint Kinase 2 (CHK2) Following AMG 436(Baseline up to 5 years)
研究者
研究点 (26)
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