A Phase 1/Phase 2 Study to Evaluate the Safety and Tolerability of MK-1088 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 27
- 试验地点
- 13
- 主要终点
- Percentage of Participants Experiencing a Dose-limiting Toxicity (DLT)
研究概览
简要总结
The study will evaluate the safety, tolerability, and pharmacokinetics (PK) of MK-1088 in monotherapy and in combination with pembrolizumab in participants with advanced solid tumors who have not responded to conventional therapy. The effect of MK-1088 on tumor size will also be examined.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Has a histologically- or cytologically-confirmed diagnosis of advanced/metastatic solid tumor by pathology report and have received, have been intolerant to, or have been ineligible for treatment known to confer clinical benefit
- •For metastatic castrate-resistant prostate cancer (mCRPC) only: (1) Must have previously received docetaxel, prior treatment with one other chemotherapy is allowed as well as up to 2 second-generation hormonal manipulations and (2) have prostate cancer progression within 6 months before screening, as determined by the investigator
- •If human immunodeficiency virus (HIV) positive, has well-controlled HIV on anti-retroviral therapy (ART)
排除标准
- •Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) before the first dose of study intervention
- •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
- •Has a history of interstitial lung disease
- •Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis
- •Has an active autoimmune disease that has required systemic treatment in the past 2 years
- •Has concurrent active Hepatitis B and Hepatitis C virus infection
- •Has HIV with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- •Has not fully recovered from any effects of major surgery without significant detectable infection
- •Has a history or current evidence of a gastrointestinal (GI) condition or impaired liver function or diseases that in the opinion of the investigator may significantly alter the absorption or metabolism of oral medications
- •Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Health Association (NYHA) Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability
- •Has a corrected QT interval using Fridericia's Correction Formula (QTcF) >470 msec
- •Has history of an allogeneic stem cell transplant or a solid organ transplant.
- •Has received prior systemic anticancer therapy including investigational agents within 4 weeks before allocation
- •Has received prior radiotherapy within 2 weeks of start of study intervention, or had radiation-related toxicities requiring corticosteroids
- •Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
- •Has a "superscan" bone scan
研究组 & 干预措施
MK-1088 100 mg
Participants received MK-1088 daily (QD) orally at 100 mg on days 1-21 of each 21-day cycle for up to 35 cycles (up to ~24 months).
干预措施: MK-1088 (Drug)
MK-1088 200 mg
Participants received MK-1088 (QD) orally at 200 mg on days 1-21 of each 21-day cycle for up to 35 cycles (up to ~24 months)
干预措施: MK-1088 (Drug)
MK-1088 400 mg
Participants received MK-1088 (QD) orally at 400 mg on days 1-21 of each 21-day cycle for up to 35 cycles (up to ~24 months)
干预措施: MK-1088 (Drug)
MK-1088 600 mg
Participants received MK-1088 (QD) orally at 600 mg on days 1-21 of each 21-day cycle for up to 35 cycles (up to ~24 months)
干预措施: MK-1088 (Drug)
MK-1088 100 mg + Pembrolizumab
Participants received MK-1088 daily (QD) orally at 100 mg on days 1-21 of each 21-day cycle plus pembrolizumab at 200 mg intravenous (IV) infusion every 3 weeks (Q3W), on Day 1 of each 21-day cycle for up to 35 cycles (up to ~24 months)
干预措施: MK-1088 (Drug)
MK-1088 100 mg + Pembrolizumab
Participants received MK-1088 daily (QD) orally at 100 mg on days 1-21 of each 21-day cycle plus pembrolizumab at 200 mg intravenous (IV) infusion every 3 weeks (Q3W), on Day 1 of each 21-day cycle for up to 35 cycles (up to ~24 months)
干预措施: Pembrolizumab (Biological)
MK-1088 200 mg + Pembrolizumab
Participants received MK-1088 daily (QD) orally at 200 mg on days 1-21 of each 21-day cycle plus pembrolizumab at 200 mg intravenous (IV) infusion every 3 weeks (Q3W), on Day 1 of each 21-day cycle for up to 35 cycles (up to ~24 months)
干预措施: MK-1088 (Drug)
MK-1088 200 mg + Pembrolizumab
Participants received MK-1088 daily (QD) orally at 200 mg on days 1-21 of each 21-day cycle plus pembrolizumab at 200 mg intravenous (IV) infusion every 3 weeks (Q3W), on Day 1 of each 21-day cycle for up to 35 cycles (up to ~24 months)
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Percentage of Participants Experiencing a Dose-limiting Toxicity (DLT)
时间窗: Up to 21 days
A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0). Per protocol participants who switched over from MK-1088 monotherapy into MK-1088 100 mg + Pembrolizumab combination therapy completed the DLT evaluation period in the monotherapy arm assigned. Percentage of participants who experienced a DLT are presented.
Percentage of Participants Experiencing an Adverse Event (AE)
时间窗: Up to ~13 months
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Safety data from participants who experienced disease progression in the monotherapy arm and crossed over into the combination arm are summarized in their initial monotherapy dose group until the time of cross over and are summarized separately thereafter. The percentage of participants who experienced an AE are presented.
Percentage of Participants Discontinuing Study Treatment Due to an AE
时间窗: Up to ~10 months
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Safety data from participants who experienced disease progression in the monotherapy arm and crossed over into the combination arm are summarized in their initial monotherapy dose group until the time of cross over and are summarized separately thereafter. The percentage of participants who discontinued study treatment due to an AE is presented.
次要结局
- Area Under the Plasma Concentration-time Curve (AUC) of MK-1088(Pre-dose and 1, 2, 4, and 8 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1; Pre-dose on Cycle 1 Day 2 and Cycle 2 Day 2; Pre-dose on Cycle 3, Cycle 4 and every 4 cycles up to ~3.5 months. Each cycle = 21 days)
- Maximum Plasma Concentration (Cmax) of MK-1088(Pre-dose and 1, 2, 4, and 8 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1; Pre-dose on Cycle 1 Day 2 and Cycle 2 Day 2; Pre-dose on Cycle 3, Cycle 4 and every 4 cycles up to ~3.5 months. Each cycle = 21 days)
- Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) or Prostate Cancer Working Group (PCWG)-Modified RECIST 1.1 as Assessed by Investigator(Up to ~13 months)