A Phase 1 Open-label Study to Evaluate the Safety and Efficacy of MK-8294 Monotherapy in Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 67
- 试验地点
- 11
- 主要终点
- Number of participants who experience one or more dose-limiting toxicities (DLTs)
研究概览
简要总结
MK-8294, the study medicine, is a type of targeted therapy designed to treat certain solid tumors. The main goals of this study are to learn about the safety of MK-8294 and if people can tolerate it and find the highest dose level of MK-8294 that people can tolerate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 main inclusion criteria include but are not limited to the following:
- •Has histologically or cytologically confirmed advanced/metastatic solid tumor; including head and neck squamous cell carcinoma, cervical squamous cell carcinoma, esophageal squamous cell carcinoma, breast cancer (triple negative breast cancer, Estrogen Receptor [ER]/progesterone receptor +, human epidermal growth factor receptor 2 negative [HER2-]), endometrial, and bladder cancer by pathology report and have previously failed standard treatment, lack standard treatment options, or are intolerant to standard treatment
- •Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
- •Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load
- •Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- •Has a history of New York Heart Association Class II or greater heart failure
- •Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related Adverse Event (irAE) (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis
- •Has ongoing radiation-related toxicities, requiring corticosteroids
- •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 (eg, thyroxine, insulin, or physiologic corticosteroid)
- •Has active infection requiring systemic therapy
- •Has history of stem cell/solid organ transplant
- •Has not adequately recovered from major surgery or have ongoing surgical complications
研究组 & 干预措施
MK-8294
Participants will receive MK-8294 monotherapy in escalating doses starting from 30 µg up to a planned 70 mg via intravenous (IV) infusion. In addition, intermediate doses may also be assessed. MK-8294 will be administered on Day 1, Day 8, and Day 15 of each cycle (each cycle = 21 days). Per protocol treatment of MK-8294 has no maximum number of cycles. Participants will be treated until any of the criteria for discontinuation of study intervention are met. Participants may also receive a cluster of differentiation 8 (CD8) positron emission tomography (PET) tracer as a part of optional PET imaging.
干预措施: MK-8294 (Drug)
MK-8294
Participants will receive MK-8294 monotherapy in escalating doses starting from 30 µg up to a planned 70 mg via intravenous (IV) infusion. In addition, intermediate doses may also be assessed. MK-8294 will be administered on Day 1, Day 8, and Day 15 of each cycle (each cycle = 21 days). Per protocol treatment of MK-8294 has no maximum number of cycles. Participants will be treated until any of the criteria for discontinuation of study intervention are met. Participants may also receive a cluster of differentiation 8 (CD8) positron emission tomography (PET) tracer as a part of optional PET imaging.
干预措施: CD8 PET Tracer (Other)
结局指标
主要结局
Number of participants who experience one or more dose-limiting toxicities (DLTs)
时间窗: Up to approximately 35 days
DLT is defined as any drug-related adverse event (AE) observed during the DLT evaluation period (up to 35 days) that results in a change to a given dose or a delay in initiating the next treatment and reported as the number of participants experiencing a DLT.
Number of Participants Who Experience an Adverse Event (AE)
时间窗: Up to approximately 2 years
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be reported.
Number of Participants Who Discontinue Study Intervention Due to an AE
时间窗: Up to approximately 2 years
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study/study treatment due to an AE will be reported.
次要结局
- Objective Response Rate (ORR)(Up to approximately 2 years)
- Area Under the Plasma Concentration-Time Curve (AUC) of MK-8294(Predose and at designated timepoints in each cycle for up to approximately 2 years (each cycle = 3 weeks))
- Minimum Concentration (Cmin) of MK-8294(Predose and at designated timepoints in each cycle for up to approximately 2 years (each cycle = 3 weeks))
- Maximum Plasma Concentration (Cmax) of MK-8294(Predose and at designated timepoints in each cycle for up to approximately 2 years (each cycle = 3 weeks))
- Time to Maximum Plasma Concentration (Tmax) of MK-8294(Predose and at designated timepoints in each cycle for up to approximately 2 years (each cycle = 3 weeks))
- Incidence of Antidrug Antibodies (ADA) to MK-8294(Predose and at designated timepoints in each cycle for up to approximately 2 years (each cycle = 3 weeks))
- Titer of ADA to MK-8294(Predose and at designated timepoints in each cycle for up to approximately 2 years (each cycle = 3 weeks))