A Phase 2, Open-label Study to Evaluate the Safety and Efficacy of MK-7684A (MK-7684 [Vibostolimab] With MK-3475 [Pembrolizumab] Coformulation) in Participants With Relapsed or Refractory Hematological Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 192
- 试验地点
- 103
- 主要终点
- Percentage of Participants With a Dose-Limiting Toxicity (DLT)
研究概览
简要总结
The purpose of the study is to determine the safety and tolerability of pembrolizumab/vibostolimab (MK-7684A) in hematological malignancies. This study will also evaluate the overall response rate (ORR), the duration of response (DOR), and disease control rate (DCR) following administration of pembrolizumab/vibostolimab. In addition, this study will characterize pharmacokinetic (PK) profile of vibostolimab (MK-7684).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •- Have confirmed relapsed/refractory classic Hodgkins Lymphoma (cHL), Primary mediastinal B-cell lymphoma (PMBCL), Follicular Lymphoma (FL), Diffuse large B-cell lymphoma (DLBCL) or Non-Hodgkins Lymphoma (NHL), or multiple myeloma (MM).
- •For PMBCL, DLBCL, FL, and MM:
- •- Must be relapsed or refractory to CAR-T-cell therapy or unable to receive it.
- •For DLBCL and NHL:
- •- Must have exhausted or be ineligible for or intolerant to all treatments, which in the opinion of the investigator are standard of care for their disease.
- •- Participants with Mantle cell lymphoma (MCL) must have received prior Bruton's tyrosine kinase inhibitor therapy.
- •All participants:
- •Have measurable disease.
- •Have adequate organ function.
- •Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before allocation.
- •Must be able to provide newly obtained bone marrow biopsy or aspirate material for disease assessment.
- •Female participants are eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of non child-bearing potential (WONCBP) OR Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle.
排除标准
- •For DLBCL and NHL:
- •- Has lymphoplasmacytic lymphomas, Waldenstrom's macroglobulinemia, chronic lymphocytic leukemia (not associated with small lymphocytic lymphoma), Burkitt (-like) lymphoma, mature T cell and NK cell neoplasms, immunodeficiency associated lymphoproliferative neoplasms, or histiocytic and dendritic cell neoplasms.
- •Has oligo-secretory myeloma, plasma cell leukemia, smoldering multiple myeloma, or monoclonal gammopathy of undetermined significance.
- •Has a history of primary amyloidosis, hyperviscosity or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
- •Has known prior or current central nervous system (CNS) involvement.
- •For Epstein Barr virus (EBV) positive DLBCL:
- •- Associated with a solid organ transplant.
- •For all participants:
- •A WOCBP who has a positive urine pregnancy test within 72 hours before study intervention allocation.
- •Has clinically significant cardiovascular disease within 12 months from first dose of study intervention.
- •Has a history of a second malignancy.
- •Any PMBCL participants that require the use of urgent cytoreductive therapy.
- •If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery before starting study intervention.
- •Has received prior radiotherapy within 2 weeks of start of study intervention.
- •Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
- •Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
- •Has a known severe hypersensitivity to MK-7684A, vibostolimab or pembrolizumab and/or any of its excipients.
- •Has a known history of Human Immunodeficiency Virus (HIV) infection.
- •Has an active autoimmune disease that has required systemic treatment in past 2 years.
- •Has an active infection requiring systemic therapy.
- •Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
- •Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks before enrollment.
- •Has dual active HBV infection (HBsAg (+) and /or detectable HBV DNA) and Hepatitis C (HCV) infection (anti-HCV Ab (+) and detectable HCV RNA) at study entry..
- •Has had an allogenic hematopoietic stem cell/solid organ transplantation within the last 5 years.
研究组 & 干预措施
Pembrolizumab/vibostolimab coformulation
Participants will receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years.
干预措施: Pembrolizumab/vibostolimab coformulation (Biological)
结局指标
主要结局
Percentage of Participants With a Dose-Limiting Toxicity (DLT)
时间窗: Up to approximately 6 weeks
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). Percentage of participants who experience a DLT per CTCAE 5.0 are reported.
Percentage of Participants Who Experienced an Adverse Event (AE)
时间窗: Up to approximately 27 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 adverse event. The number of participants who experience an AE are reported.
Percentage of Participants Who Discontinued Study Treatment Due to an AE
时间窗: Up to approximately 24 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 adverse event. The number of participants discontinued from the study treatment due to an AE are reported.
次要结局
- Objective Response Rate (ORR) as Assessed by Lugano 2014 Classification (Cohorts A-D & F)(Up to approximately 37 months)
- ORR as Assessed by the 2016 International Myeloma Working Group (IMWG) Response Criteria (Cohort E)(Up to approximately 37 months)
- Duration of Response (DOR) as Assessed by Lugano 2014 Classification (Cohorts A-D & F)(Up to approximately 37 months)
- DOR as Assessed by 2016 IMWG Response Criteria (Cohort E)(Up to approximately 37 months)
- Disease Control Rate (DCR) as Assessed by Lugano 2014 Classification (Cohorts A-D & F)(Up to approximately 37 months)
- DCR as Assessed by 2016 IMWG Response Criteria (Cohort E)(Up to approximately 37 months)
- Lowest Plasma Concentration (Ctrough) of Vibostolimab(Predose at Cycles 1, 3, 7, 11, 15, 19, 23, 27 and 31. Cycle = 3 weeks)
- Maximum Concentration (Cmax) of Vibostolimab(Postdose: after end of infusion (up to ~10 minutes) at Cycles 1 and 8. Cycle = 3 weeks)