A Phase 1 Open-label, Multicenter Study of MK-6837 as Monotherapy and Combination Therapy in Participants With Advanced/Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 7
- 主要终点
- Number of participants who experience one or more dose-limiting toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy of MK-6837, administered as a monotherapy and in combination with pembrolizumab (MK-3475), in participants with histologically or cytologically confirmed advanced/metastatic solid tumors that have not responded to conventional therapy. There will not be any hypothesis testing in the study.
As of Amendment 04 (effective date: 18-Dec-2025), there are no pharmacokinetic (PK) secondary outcome measures in this study.
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
- •The main inclusion criteria include but are not limited to the following:
- •Histologically or cytologically confirmed solid tumor by pathology report that is advanced or metastatic
- •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 before allocation
- •Participants with history of Hepatitis C Virus (HCV) infection are eligible if HCV viral load is undetectable at screening
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from any Adverse Events (AEs) that were due to cancer therapeutics administered more than 4 weeks earlier
- •History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
- •Has clinically significant cardiovascular disease
- •HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- •Received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
- •Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related AE (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
- •Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
- •Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed
- •Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of study intervention
- •Known additional malignancy that is progressing or has required active treatment within the past 2 years
- •Known active Central Nervous System (CNS) metastases and/or carcinomatous meningitis
- •Active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy
- •History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- •Active infection requiring systemic therapy
- •History of allogeneic tissue/solid organ transplant
- •Participants who have not adequately recovered from major surgery or have ongoing surgical complications
研究组 & 干预措施
Arm 2: MK-6837 + Pembrolizumab Combination Therapy
Participants receive escalating doses of MK-6837 via IV infusion Q3W (Day 1 of every 21-day cycle) until progressive disease or discontinuation PLUS 200mg of pembrolizumab via IV infusion Q3W (Day 1 of every 21-day cycle) for up to 35 administrations (up to ~2 years).
干预措施: MK-6837 (Biological)
Arm 1: MK-6837 Monotherapy
Participants receive escalating doses of MK-6837 via intravenous (IV) infusion once every 3 weeks (Q3W) (Day 1 of every 21-day cycle) until progressive disease or discontinuation.
干预措施: Rescue Medications (Drug)
Arm 2: MK-6837 + Pembrolizumab Combination Therapy
Participants receive escalating doses of MK-6837 via IV infusion Q3W (Day 1 of every 21-day cycle) until progressive disease or discontinuation PLUS 200mg of pembrolizumab via IV infusion Q3W (Day 1 of every 21-day cycle) for up to 35 administrations (up to ~2 years).
干预措施: Rescue Medications (Drug)
Arm 2: MK-6837 + Pembrolizumab Combination Therapy
Participants receive escalating doses of MK-6837 via IV infusion Q3W (Day 1 of every 21-day cycle) until progressive disease or discontinuation PLUS 200mg of pembrolizumab via IV infusion Q3W (Day 1 of every 21-day cycle) for up to 35 administrations (up to ~2 years).
干预措施: Pembrolizumab (Biological)
Arm 1: MK-6837 Monotherapy
Participants receive escalating doses of MK-6837 via intravenous (IV) infusion once every 3 weeks (Q3W) (Day 1 of every 21-day cycle) until progressive disease or discontinuation.
干预措施: MK-6837 (Biological)
结局指标
主要结局
Number of participants who experience one or more dose-limiting toxicities (DLTs)
时间窗: Cycle 1 (Up to approximately 21 days); each cycle is 21 days.
The following events will be considered a DLT unless clearly due to underlying disease or extraneous causes: Grade 4 neutropenia lasting \>7 days; Grade 3 or higher thrombocytopenia associated with clinically significant bleeding, regardless of duration; All Grade 3 or higher nonhematologic toxicities (with exceptions); Any abnormality that results in a drug induced liver injury; Febrile neutropenia Grade 3 or 4; Prolonged delay (\>2 weeks) in initiating treatment after the first 21 days due to intervention-related toxicity; Any intervention-related toxicity that causes the participant to discontinue intervention during the first 21 days; Grade 5 toxicity. The number of participants who experience a DLT will be presented.
Number of participants who experience one or more dose-limiting toxicities (DLTs)
时间窗: Cycle 1 (Up to approximately 21 days); each cycle is 21 days.
The following events will be considered a DLT unless clearly due to underlying disease or extraneous causes: Grade 4 neutropenia lasting \>7 days; Grade 3 or higher thrombocytopenia associated with clinically significant bleeding, regardless of duration; All Grade 3 or higher nonhematologic toxicities (with exceptions); Any abnormality that results in a drug induced liver injury; Febrile neutropenia Grade 3 or 4; Prolonged delay (\>2 weeks) in initiating treatment after the first 21 days due to intervention-related toxicity; Any intervention-related toxicity that causes the participant to discontinue intervention during the first 21 days; Grade 5 toxicity. The number of participants who experience a DLT will be presented.
Number of participants who experience one or more adverse events (AEs)
时间窗: Up to approximately 35 months
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.
Number of participants who discontinue study intervention due to an AE
时间窗: Up to approximately 35 months
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
未报告次要终点