A Phase 1, Open-label, Multicenter Study of the Safety, Pharmacokinetics, and Pharmacodynamics of MK-4464 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced/Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 6
- 主要终点
- Number of Participants Who Discontinue Study Treatment Due to an AE
研究概览
简要总结
The purpose of this study is to assess the safety, pharmacokinetics, and preliminary efficacy of MK-4464 as monotherapy and in combination with pembrolizumab in participants with advanced/metastatic 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 —（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:
- •Have a histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report and have received, been intolerant to, been ineligible for, or refused all treatment known to confer clinical benefit
- •Must submit a baseline tumor sample for analysis
- •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
- •Human immunodeficiency virus (HIV) infected participants must have well controlled HIV on antiretroviral therapy (ART)
- •Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load before randomization.
排除标准
- •The key Exclusion Criteria include but are not limited to the following:
- •Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) before the first dose of study intervention or has not recovered to CTCAE Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier
- •Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
- •Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has an active infection requiring therapy
- •History of an allogenic stem cell transplant or a solid organ transplant
- •Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- •Has an active autoimmune disease that has required systemic treatment in the past 2 years
- •HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- •Has known psychiatric or substance abuse disorders that would interfere with the participant's ability to cooperate with the requirements of the study
- •Has not fully recovered from any effects of major surgery without significant detectable infection
- •Has received radiation therapy to the lung that is >30 gray (Gy) within 6 months of the first dose of study treatment
- •Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
- •Is currently participating and receiving study intervention in a study of an investigational agent or has participated and received study intervention in a study of an investigational agent or has used an investigational device within 28 days
研究组 & 干预措施
MK-4464
Participants will receive an intravenous (IV) infusion of MK-4464 administered in escalating doses every 3 weeks for up to 35 cycles. Escalation to subsequent MK-4464 doses will be based on safety of previous dose.
干预措施: MK-4464 (Biological)
MK-4464 + Pembrolizumab
Participants will receive an IV infusion of MK-4464 administered in escalating doses and a 200 mg IV infusion of Pembrolizumab every 3 weeks for up to 35 cycles. Escalation to subsequent MK-4464 doses will be based on safety of MK-4464 monotherapy arm.
干预措施: MK-4464 (Biological)
MK-4464 + Pembrolizumab
Participants will receive an IV infusion of MK-4464 administered in escalating doses and a 200 mg IV infusion of Pembrolizumab every 3 weeks for up to 35 cycles. Escalation to subsequent MK-4464 doses will be based on safety of MK-4464 monotherapy arm.
干预措施: Pembrolizumab (Biological)
MK-4464 + Pembrolizumab + Zirconium 89 (89Zr)-MK-4464
Participants will receive an IV infusion of 89Zr-MK-4464 + IV infusion of MK-4464 on Cycle 1 Day 1, followed by an IV infusion of MK-4464 + a 200 mg IV infusion of pembrolizumab starting on Cycle 2 Day 1 and every 3 weeks for up to 35 cycles. Each cycle=3 weeks. MK-4464 doses will be based on safety of MK-4464 monotherapy arm. Participants may receive a 200 mg IV infusion of pembrolizumab on cycle 36.
干预措施: MK-4464 (Biological)
MK-4464 + Pembrolizumab + Zirconium 89 (89Zr)-MK-4464
Participants will receive an IV infusion of 89Zr-MK-4464 + IV infusion of MK-4464 on Cycle 1 Day 1, followed by an IV infusion of MK-4464 + a 200 mg IV infusion of pembrolizumab starting on Cycle 2 Day 1 and every 3 weeks for up to 35 cycles. Each cycle=3 weeks. MK-4464 doses will be based on safety of MK-4464 monotherapy arm. Participants may receive a 200 mg IV infusion of pembrolizumab on cycle 36.
干预措施: Pembrolizumab (Biological)
MK-4464 + Pembrolizumab + Zirconium 89 (89Zr)-MK-4464
Participants will receive an IV infusion of 89Zr-MK-4464 + IV infusion of MK-4464 on Cycle 1 Day 1, followed by an IV infusion of MK-4464 + a 200 mg IV infusion of pembrolizumab starting on Cycle 2 Day 1 and every 3 weeks for up to 35 cycles. Each cycle=3 weeks. MK-4464 doses will be based on safety of MK-4464 monotherapy arm. Participants may receive a 200 mg IV infusion of pembrolizumab on cycle 36.
干预措施: 89Zr-MK-4464 (Drug)
结局指标
主要结局
Number of Participants Who Discontinue Study Treatment Due to an AE
时间窗: Up to approximately 24 months
An AE is defined as 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 treatment due to an AE will be presented.
Number of Participants Who Experience At Least One adverse event (AE)
时间窗: Up to approximately 27 months
An AE is defined as 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 at least one AE will be presented.
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
时间窗: Up to approximately 21 days
A DLT is any toxicity assessed by the investigator to be possibly, probably, or definitely related to study intervention administration that results in a change to a given dose or a delay in initiating the next cycle. All toxicities will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).
次要结局
- Minimum Plasma Concentration (Cmin) of MK-4464(Once daily on Day 2, 3, 5, 8, 15 of Cycle 1 and 4, Pre-dose and immediately Post-dose Day 1 Cycle 1, 2, 3, 4, Pre-dose Day 1 Cycles 5, 6, 7, 8, and every 4 cycles thereafter through Cycle 35, 30 days post last dose (up to ~25 months); Cycle = 21 days)
- Maximum Plasma Concentration (Cmax) of MK-4464(Once daily on Day 2, 3, 5, 8, 15 of Cycle 1 and 4, Pre-dose and immediately Post-dose Day 1 Cycle 1, 2, 3, 4, Pre-dose Day 1 Cycles 5, 6, 7, 8, and every 4 cycles thereafter through Cycle 35, 30 days post last dose (up to ~25 months); Cycle = 21 days)
- Objective Response Rate (ORR)(Up to 24 months)
- Area Under the Plasma Concentration-Time Curve (AUC) of MK-4464(Once daily on Day 2, 3, 5, 8, 15 of Cycle 1 and 4, Pre-dose and immediately Post-dose Day 1 Cycle 1, 2, 3, 4, Pre-dose Day 1 Cycles 5, 6, 7, 8, and every 4 cycles thereafter through Cycle 35, 30 days post last dose (up to ~25 months); Cycle = 21 days)