Phase Ib Trial of Pembrolizumab (MK-3475) in Combination With Dinaciclib (MK-7965) in Subjects With Hematologic Malignancies (KEYNOTE-155).
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 75
- 主要终点
- Number of Participants With Dose Limiting Toxicity (DLT)
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) used in combination with dinaciclib (MK-7965) in the treatment of relapsed or refractory chronic lymphocytic leukemia (rrCLL), multiple myeloma (rrMM), or diffuse large B-cell lymphoma (rrDLBCL).
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
- •Females must not be pregnant (negative urine or serum human chorionic gonadotropin test within 72 hours of study start)
- •Female and male participants of reproductive potential must agree to use adequate contraception starting from the first dose of study medication, throughout the study period, and for up to 120 days after the last dose of study medication
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Cardiac function suitable for protocol-required hydration as determined by the investigator and/or cardiologist
- •Must be able to provide biopsy specimens obtained ≤3 months for biomarker analysis. If bone marrow biopsy was performed 3 months before screening but subject had anti-cancer treatment after biopsy, the bone marrow biopsy and aspiration should be repeated
- •Relapsed or refractory chronic lymphocytic leukemia (rrCLL) participants:
- •Must have a confirmed diagnosis of CLL defined by 2008 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
- •Must have received one prior therapy for CLL
- •Must meet one or more of the consensus criteria for initiating treatment
- •Relapsed or refractory multiple myelolma (rrMM) participants:
- •Must have a confirmed diagnosis of active MM
- •Must have undergone prior treatment with ≥2 treatment lines of anti-myeloma therapy and failed last line of treatment (disease progression ≤60 days of completion of last therapy)
- •Must have failed prior anti-myeloma treatments that have included an immunomodulatory drug (IMiD) (pomalidomide, lenalidomide, or thalidomide) AND proteasome inhibitor (bortezomib, carfilzomib, or ixazomib) alone or in combination
- •Diffuse large B-cell lymphoma (rrDLBCL) participants:
- •Must have a confirmed diagnosis of DLBCL and have progressed following ≥2 lines of previous therapy, after autologous stem cell transplant, or not a candidate for autologous stem cell transplant
- •Must have measurable disease (≥1 lesion that is >15 mm in the longest diameter or by >10 mm in the short axis)
排除标准
- •Has been treated with a cytochrome P450 3A4 (CYP3A4) strong inhibitor or inducer within 7 days of enrollment
- •Has been treated with anti-cancer therapy or thoracic radiation therapy within 14 days
- •Has known clinically active central nervous system (CNS) involvement
- •Has a known history of immunosuppression or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days
- •Has had prior anti-cancer monoclonal antibody within 4 weeks of Study Day 1 or who has not recovered from adverse events due to agents administered >4 weeks earlier
- •Has undergone prior allogeneic hematopoetic stem cell transplantation within the last 5 years
- •Has a known additional malignancy that is progressing or requires active treatment
- •Has active autoimmune disease that has required systemic treatment in past 2 years
- •Has an active infection requiring intravenous systemic therapy
- •Has received prior therapy with an anti-programmed cell death-1 (PD-1), anti-programmed cell death ligand (PD-L) 1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) or chimeric antigen receptor (CAR)-T cell therapy or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
- •Has been previously treated with a cyclin-dependent kinase (CDK) inhibitor
- •Has a known history of Human Immunodeficiency Virus (HIV) infection
- •Has a known history of or is positive for hepatitis B (hepatitis B surface antigen reactive) or hepatitis C (hepatitis C virus RNA [qualitative] is detected)
- •Has received a live vaccine within 30 days prior to the first dose of trial treatment
- •Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
- •Has known current symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
- •Relapsed or refractory chronic lymphocytic leukemia (rrCLL) participants:
- •Has Richter's Transformation
- •Relapsed or refractory multiple myelolma (rrMM) participants:
- •Participants with non-secretory or oligo-secretory myeloma, plasma cell leukemia or Waldenström's macroglobulinemia
- •History of primary amyloidosis, hyperviscosity or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- •Diffuse large B-cell lymphoma (rrDLBCL) participants:
- •Participants with primary mediastinal B-cell lymphoma (PMBCL)
- •Has Richter's Transformation
研究组 & 干预措施
rrCLL Cohort
Participants with refractory chronic lymphocytic leukemia (rrCLL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days.
干预措施: pembrolizumab (Biological)
rrCLL Cohort
Participants with refractory chronic lymphocytic leukemia (rrCLL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days.
干预措施: dinaciclib (Drug)
rrMM Cohort
Participants with relapsed or refractory multiple myeloma (rrMM) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days.
干预措施: pembrolizumab (Biological)
rrMM Cohort
Participants with relapsed or refractory multiple myeloma (rrMM) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days.
干预措施: dinaciclib (Drug)
rrDLBCL Cohort
Participants with relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days.
干预措施: pembrolizumab (Biological)
rrDLBCL Cohort
Participants with relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days.
干预措施: dinaciclib (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicity (DLT)
时间窗: Up to 42 days
DLTs consisted of the following if observed during treatment Cycles 1 or 2 and assessed by investigator to be possibly, probably, or definitely related to pembrolizumab or dinaciclib: grade 4 non-laboratory nonhematologic toxicity; grade 4 hematologic toxicity lasting \>7 days (except thrombocytopenia); grade 4 thrombocytopenia of any duration; grade 3 thrombocytopenia if associated with bleeding; any grade 3 non-laboratory nonhematologic toxicity, except grade 3 nausea, vomiting, or diarrhea, which was not considered a DLT unless lasting more than 3 days despite optimal supportive care; Grade 3 or Grade 4 nonhematologic laboratory abnormality that required medical intervention, led to hospitalization, or persisted for \>1 week; grade 3 or 4 febrile neutropenia; any drug-related AE that caused participant to discontinue treatment during Cycles 1 or 2; grade 5 toxicity; treatment-related toxicity that caused a \>2-week delay in initiation of treatment Cycle 2 or 3. Each cycle was 21 days.
Number of Participants Who Experienced an Adverse Event
时间窗: Up to approximately 582 days
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE was presented.
Number of Participants Who Discontinued Treatment Due to an Adverse Event
时间窗: Up to 492 days
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study drug due to an adverse event is presented.
次要结局
- Objective Response Rate (ORR)(Up to approximately 26 months)
- Duration of Response (DOR)(Up to approximately 26 months)
- Progression-Free Survival (PFS)(Up to approximately 26 months)
- Overall Survival (OS)(Up to approximately 44 months)