A Phase 1 Open-label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK-4700 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 7
- 主要终点
- Dose-Limiting Toxicity (DLT)
研究概览
简要总结
The goal of this study is to learn about the safety of different doses of MK-4700 and if people tolerate them. The study will also measure what happens in a person's body over time when MK-4700 is given alone or with pembrolizumab (MK-3475) in order to find a dose that is safe, tolerated, and may work to treat certain types of cancer.
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
- •The key inclusion criteria include but are not limited to the following:
- •Has histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report who have experienced disease progression on or after prior anti-cancer treatments, or been intolerant to, or refused all treatment known to confer clinical benefit
- •Has head and neck squamous cell carcinoma (HNSCC), melanoma (cutaneous), non-small cell lung cancer (NSCLC), cervical cancer, triple negative breast cancer (TNBC), urothelial carcinoma (UC), or renal cell carcinoma (RCC; clear cell, papillary)
- •If human immunodeficiency virus (HIV) infected, must have well controlled HIV on antiretroviral therapy (ART)
- •Has normal cardiac function
排除标准
- •The key exclusion criteria include but are not limited to the following:
- •If HIV-infected with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- •Has known additional malignancy that is progressing or has required active treatment within the past 2 years
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy
- •Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids
- •Has current pneumonitis/interstitial lung disease
- •Has active infection requiring systemic therapy
- •Has known history of Hepatitis B (defined as Hepatitis B surface antigen reactive) or known active Hepatitis C virus infection
- •Has had an allogeneic tissue/solid organ transplant in the last 5 years
研究组 & 干预措施
Arm 1: MK-4700
Participants receive escalating doses every three weeks (Q3W) of MK-4700 for a maximum of 35 cycles (approximately 2 years; cycles are 21 days in length). Eligible participants enrolled in Arm 1 who experience progressive disease (PD) may cross over to Arm 2 to receive MK-4700 and pembrolizumab combination therapy.
干预措施: MK-4700 (Biological)
Arm 2: MK-4700 + Pembrolizumab
Participants will receive MK-4700 and pembrolizumab Q3W for up to 35 cycles (approximately 2 years) or until PD, death, toxicity, or withdrawal of consent.
干预措施: MK-4700 (Biological)
Arm 2: MK-4700 + Pembrolizumab
Participants will receive MK-4700 and pembrolizumab Q3W for up to 35 cycles (approximately 2 years) or until PD, death, toxicity, or withdrawal of consent.
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Dose-Limiting Toxicity (DLT)
时间窗: Cycle 1 (up to 21 days)
The occurrence of any of the following toxicities during Cycle 1 will be considered a DLT, if assessed by the investigator related to study intervention administration: * Grade 4 nonhematologic toxicity * Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia * Any nonhematologic AE ≥Grade 3 in severity, with exceptions * Any Grade 3 or Grade 4 nonhematologic laboratory value, as with pre-specified exceptions * Any Grade 3 or Grade 4 laboratory abnormalities, with the exceptions * Febrile neutropenia Grade 3 or Grade 4 * Prolonged delay (\>2 weeks) in initiating Cycle 2 due to intervention-related toxicity * Any study drug toxicity that causes the participant to discontinue study drug during Cycle 1 * Missing \>25% of MK-4700 doses as a result of drug-related AEs during the first cycle * Grade 5 toxicity
Percentage of Participants Who Experience an Adverse Event (AE)
时间窗: Up to approximately 4.5 years
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Percentage of Participants who Discontinue Study Treatment Due to an AE
时间窗: Up to approximately 4.5 years
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
次要结局
- Maximum Plasma Concentration (Cmax) of MK-4700(Predose and at prespecified time points during Cycles 1, 2, 3, 4, 5, 6, 7, and 10 up to approximately 7 months (Cycle length is 21 days))
- Area Under the Concentration-Time Curve of MK-4700(Predose and at prespecified time points during Cycles 1, 2, 3, 4, 5, 6, 7, and 10 up to approximately 7 months (Cycle length is 21 days))
- Minimum Plasma Concentration (Cmin) of MK-4700(Predose and at prespecified time points during Cycles 1, 2, 3, 4, 5, 6, 7, and 10 up to approximately 7 months (Cycle length is 21 days))