Phase Ib Trial of Pembrolizumab (MK-3475) in Combination With Dinaciclib (MK-7965) in Subjects With Hematologic Malignancies (KEYNOTE-155).
Overview
- Phase
- Phase 1
- Intervention
- pembrolizumab
- Conditions
- rrCLL
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 75
- Primary Endpoint
- Number of Participants With Dose Limiting Toxicity (DLT)
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
Brief Summary
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •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:
Exclusion Criteria
- •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
Arms & Interventions
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.
Intervention: pembrolizumab
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.
Intervention: dinaciclib
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.
Intervention: pembrolizumab
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.
Intervention: dinaciclib
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.
Intervention: pembrolizumab
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.
Intervention: dinaciclib
Outcomes
Primary Outcomes
Number of Participants With Dose Limiting Toxicity (DLT)
Time Frame: 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
Time Frame: 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
Time Frame: 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.
Secondary Outcomes
- 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)