A Phase 1 Trial of MK-1248 as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors.
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 37
- 主要终点
- Number of Participants Experiencing a Dose-Limiting Toxicity (DLT)
研究概览
简要总结
In this study, participants with advanced solid tumors were assigned to receive escalating doses of either MK-1248 alone or MK-1248 in combination with pembrolizumab (MK-3475). This study used the number of dose-limiting toxicities (DLTs) at each dose level to find and confirm the maximum tolerated dose (or maximum administered dose) for MK-1248 alone and in combination with pembrolizumab.
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
- •Histologically- or cytologically-confirmed metastatic solid tumor for which there is no available therapy that may convey clinical benefit
- •Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria
- •Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
- •Adequate organ function
- •Female participants of childbearing potential should be willing to use adequate contraception for the course of the study through 120 days after the last dose of study medication
- •Male participants should agree to use adequate contraception starting with the first dose of study therapy through 180 days after the last dose of study medication
- •Can submit a baseline tumor sample
排除标准
- •Has had chemotherapy, radiation, or biological cancer therapy within 4 weeks prior to the first dose of study medication, or not recovered from adverse events due to cancer therapeutics administered more than 4 weeks earlier
- •Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study medication
- •Previous treatment with another agent targeting the glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) receptor
- •Previous treatment with an immunomodulatory therapy and was discontinued from that therapy due to an immune-related adverse event
- •Expected to require any other form of antineoplastic therapy while on study
- •On chronic systemic steroid therapy in excess of replacement doses, or on any other form of immunosuppressive medication
- •History of a previous, additional malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 5 years with the exception of successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Severe hypersensitivity reaction to treatment with another monoclonal antibody
- •Active autoimmune disease or a documented history of autoimmune disease with the exception of vitiligo or resolved childhood asthma/atopy, or endocrine deficiency following treatment with an immunomodulatory agent
- •Active infection requiring therapy
- •Active or a history of non-infectious pneumonitis
- •Prior stem cell or bone marrow transplant
- •Known history of human immunodeficiency virus (HIV), active chronic or acute hepatitis B or C
- •Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
- •Regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol), at the time of signing informed consent
- •Symptomatic ascites or pleural effusion
- •Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study through 180 days after the last dose of study medication
- •Major surgery within 16 weeks prior to screening
- •Live vaccine within 30 days prior to first dose of study medication
研究组 & 干预措施
MK-1248 + Pembrolizumab
Participants received escalating doses of MK-1248 at assigned dose (dose range: 0.12 mg to 60 mg MK-1248) via IV infusion on Day 1 of each 21-day cycle for a maximum of 4 cycles (up to ~3 months) PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to ~24 months).
干预措施: pembrolizumab (Biological)
MK-1248 + Pembrolizumab
Participants received escalating doses of MK-1248 at assigned dose (dose range: 0.12 mg to 60 mg MK-1248) via IV infusion on Day 1 of each 21-day cycle for a maximum of 4 cycles (up to ~3 months) PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to ~24 months).
干预措施: MK-1248 (Biological)
MK-1248
Participants received escalating doses of MK-1248 at assigned dose (dose range: 0.12 mg to 170 mg MK-1248) via intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 4 cycles (up to ~3 months).
干预措施: MK-1248 (Biological)
结局指标
主要结局
Number of Participants Experiencing a Dose-Limiting Toxicity (DLT)
时间窗: Cycle 1 (Up to 21 days)
The occurrence of any of the following toxicities during Cycle 1 (21 days), if possibly, probably or definitely related to study treatment, was considered a DLT: 1. Grade 4 non-hematological toxicity 2. Grade 4 hematological toxicity lasting \>7 days, except thrombocytopenia a. Grade 4 thrombocytopenia of any duration b. Grade 3 thrombocytopenia is a DLT if associated with bleeding 3. Any Grade 3 non-hematological toxicity, with the exceptions 4. Any Grade 3 or Grade 4 non-hematological laboratory abnormality, if medical intervention was required, or abnormality led to hospitalization, or abnormality persisted for \>1 week 5. Febrile neutropenia Grade 3 or Grade 4 6. Any drug-related AE which caused participant to discontinue study treatment during Cycle 1 7. Grade 5 toxicity 8. Any treatment-related toxicity which caused a \>2-week delay in initiation of Cycle 2.
次要结局
- Maximum Concentration (Cmax) of MK-1248 in Serum(At designated timepoints (Up to ~3 months))
- Maximum Concentration (Cmax) of Glucocorticoid-induced Tumor Necrosis Factor Receptor-related Protein (GITR) Receptor Target Engagement(At designated timepoints (Up to ~4.5 months))
- Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) of MK-1248 in Serum(At designated timepoints (Up to ~3 months))
- Trough Concentration (Ctrough) of MK-1248 in Serum(At designated timepoints (Up to ~3 months))
- Trough (Minimum) Concentration (Ctrough) of Glucocorticoid-induced Tumor Necrosis Factor Receptor-related Protein (GITR) Receptor Target Engagement(At designated timepoints (Up to ~4.5 months))