A Phase I/II Study of Pembrolizumab (MK-3475) in Japanese Pediatric Participants With Specific Solid Tumors or Lymphomas, or in Japanese Adult Participants With Advanced Merkel Cell Carcinoma (KEYNOTE-G21)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 7
- 主要终点
- Arm 1: Number of Participants Who Experience an Adverse Event (AE)
研究概览
简要总结
Researchers are looking for new ways to treat people with solid tumors, lymphomas (blood cancers), and a certain type of skin cancer. The goals of this study are to learn:
- About the safety of pembrolizumab (the study medicine) and if people tolerate it
- What happens to different doses of pembrolizumab in a person's body over time
- How the cancer responds (gets smaller or goes away) to treatment
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
- Single (Outcomes Assessor)
盲法说明
No blinding for Arm 1. Outcomes assessor blinded for Arm 2.
入排标准
- 年龄范围
- 6 Months 至 —（Child, 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:
- •For participants with relapsed or refractory classical Hodgkin lymphoma (cHL) or primary mediastinal large B-cell lymphoma (PMBCL)
- •Has a confirmed diagnosis of relapsed or refractory cHL or PMBCL after the most recent therapy
- •Has radiographically measurable disease per Lugano classification
- •For participants with completely resected melanoma:
- •Has surgically completely resected and histologically/pathologically confirmed diagnosis of Stage IIB, IIC, III or IV cutaneous melanoma
- •Has not received any prior systemic therapy for their melanoma beyond surgical resection
- •All suspicious lesions amenable to biopsy are confirmed negative for malignancy
- •For participants with locally advanced or metastatic melanoma:
- •Has histologically confirmed diagnosis of locally advanced (unresectable Stage III) or metastatic (Stage IV) melanoma (including acral) not amenable to local therapy
- •Has radiographically measurable lesion(s) as defined by RECIST 1.1
- •For participants with microsatellite instability-high (MSI-H)/mismatch repair deficiency (dMMR) solid tumors:
- •Has histologically/cytologically documented, locally-advanced, or metastatic solid malignancy that is incurable and has either (a) failed prior standard therapy, (b) for which no standard therapy exists, or (c) standard therapy is not considered appropriate by the participant and treating physician
- •Has a documented positive local MSI-H or dMMR test result
- •Has radiographically measurable disease based on RECIST 1.1
- •For participants with tumor mutational burden-high (TMB-H) solid tumors:
- •Has histologically/cytologically documented, locally-advanced, or metastatic solid malignancy that is incurable and has either (a) failed prior standard therapy, (b) for which no standard therapy exists, or (c) standard therapy is not considered appropriate by the participant and treating physician
- •Has radiographically measurable disease based on RECIST 1.1
- •For participants with MCC:
- •Has histologically confirmed diagnosis of locoregional MCC that has recurred following standard locoregional therapy with surgery and/or radiation therapy and is not amenable to local therapy or metastatic MCC (Stage IV)
- •Has radiographically measurable disease based on RECIST 1.1
- •For participants with MCC:
- •Has been untreated for advanced or metastatic disease
- •Arm 1 & Arm 2:
- •Life expectancy of >3 months (Arm 1) or >6 months (Arm 2)
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Has known additional malignancy that is progressing or has required active treatment
- •Has known active (central nervous system) CNS metastases and/or carcinomatous meningitis
- •Has active autoimmune disease that has required systemic treatment in past 2 years
- •Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- •Has active infection requiring systemic therapy
- •Has known history of human immunodeficiency virus (HIV) infection
- •Has known history of Hepatitis B infection or known active Hepatitis C virus
- •Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic stem cell transplantation within the last 5 years
- •Has not adequately recovered from major surgery or has ongoing surgical complications
研究组 & 干预措施
Arm 2: Pembrolizumab in Adult Participants with Merkel Cell Carcinoma (MCC)
Adult participants with MCC receive 400 mg pembrolizumab via IV infusion on Day 1 of each 42 day (6 week) cycle, for up to 18 cycles.
干预措施: Pembrolizumab (Biological)
Arm 1: Pembrolizumab in Pediatric Participants with Solid Tumors or Lymphomas
Pediatric participants with solid tumors or lymphomas receive 2 mg/kg pembrolizumab via intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21 day cycle for up to 17 or 35 cycles.
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Arm 1: Number of Participants Who Experience an Adverse Event (AE)
时间窗: Up to approximately 28 months
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. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study intervention. The number of participants with solid tumors or lymphomas who experience an AE will be reported.
Arm 1: Number of Participants Who Discontinue Study Treatment Due To an AE
时间窗: Up to approximately 25 months
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. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study intervention. The number of participants with solid tumors or lymphomas who discontinue study treatment due to an AE will be reported.
Arm 1: Area Under the Concentration-Time Curve (AUC) of Pembrolizumab
时间窗: Predose at Cycle 1, 2, 4, 8 and every 4 cycles thereafter up to 35 cycles; postdose at Cycle 1 and Cycle 8 (a cycle is 21 days)
AUC is defined as the area under the concentration-time curve of pembrolizumab. Blood samples will be collected at specified intervals for the determination of AUC. AUC in participants with solid tumors or lymphomas will be reported.
Arm 1: Maximum Concentration (Cmax) of Pembrolizumab
时间窗: Predose at Cycle 1, 2, 4, 8 and every 4 cycles thereafter up to 35 cycles; postdose at Cycle 1 and Cycle 8 (a cycle is 21 days)
Cmax is defined as the maximum concentration of pembrolizumab reached. Blood samples will be collected at pre-specified intervals for the determination of Cmax. Cmax in participants with solid tumors or lymphomas will be reported.
Arm 1: Minimum Plasma Concentration (Cmin) of Pembrolizumab
时间窗: Predose at Cycle 1, 2, 4, 8 and every 4 cycles thereafter up to 35 cycles; postdose at Cycle 1 and Cycle 8 (a cycle is 21 days)
Cmin is defined as the minimum concentration of pembrolizumab observed in plasma after its administration and just prior to administration of a subsequent dose. Blood samples will be collected at pre-specified timepoints to determine Cmin. Cmin in participants with solid tumors or lymphomas will be reported.
Arm 2: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR)
时间窗: Up to approximately 37 months
ORR is defined as complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by blinded independent central review (BICR). ORR in participants with Merkel cell carcinoma will be reported.
次要结局
- Arm 1: ORR per RECIST 1.1 by Investigator Assessment(Up to approximately 46 months)
- Arm 1: ORR per Lugano Classification by Investigator Assessment(Up to approximately 46 months)
- Arm 1: Duration of Response (DOR) per RECIST 1.1 by Investigator Assessment(Up to approximately 46 months)
- Arm 1: DOR per Lugano Classification by Investigator Assessment(Up to approximately 46 months)
- Arm 1: Disease Control (DCR) per RECIST 1.1 by Investigator Assessment(Up to approximately 46 months)
- Arm 1: DCR per Lugano Classification by Investigator Assessment(Up to approximately 46 months)
- Arm 1: Progression-free Survival (PFS) per RECIST 1.1 by Investigator Assessment(Up to approximately 46 months)
- Arm 1: PFS per Lugano Classification by Investigator Assesment(Up to approximately 46 months)
- Arm 1: Relapse-free Survival (RFS) per RECIST 1.1 by Investigator Assessment(Up to approximately 46 months)
- Arm 1: Distant Metastasis-free Survival (DMFS) per RECIST 1.1 by Investigator Assessment(Up to approximately 46 months)
- Arm 1: Overall Survival (OS)(Up to approximately 46 months)
- Arm 1: Number of Participants with Anti-Drug Antibodies (ADAs) Against Pembrolizumab(Predose at Cycle 1, 2, 4, 8 and every 4 cycles thereafter up to 35 cycles (a cycle is 21 days))
- Arm 2: ORR per RECIST 1.1 by Investigator Assessment(Up to approximately 46 months)
- Arm 2: DOR per RECIST 1.1 by BICR(Up to approximately 46 months)
- Arm 2: DOR per RECIST 1.1 by Investigator Assessment(Up to approximately 46 months)
- Arm 2: DCR per RECIST 1.1 by BICR(Up to approximate ly 46 months)
- Arm 2: DCR per RECIST 1.1 by Investigator Assessment(Up to approximately 46 months)
- Arm 2: PFS per RECIST 1.1 by BICR(Up to approximately 46 months)
- Arm 2: PFS per RECIST 1.1 by Investigator Assesment(Up to approximately 46 months)
- Arm 2: OS(Up to approximately 46 months)
- Arm 2: Cmax of Pembrolizumab(Predose at Cycles 1-4, and every 2 cycles thereafter up to 18 cycles; postdose at Cycle 1 and Cycle 3 (a cycle is 42 days))
- Arm 2: Cmin of Pembrolizumab(Predose at Cycles 1-4, and every 2 cycles thereafter up to 18 cycles; postdose at Cycle 1 and Cycle 3 (a cycle is 42 days))
- Arm 2: Number of Participants Who Experience an Adverse Event (AE)(Up to approximately 28 months)
- Arm 2: Number of Participants Who Discontinue Study Treatment Due To an AE(Up to approximately 25 months)