Study of Pembrolizumab (MK-3475) in Combination With Dinaciclib (MK-7965) in Hematologic Malignancies (MK-3475-155/KEYNOTE-155)
rrCLL, rrMM, rrDLBCL
About this trial
This is an interventional treatment trial for rrCLL
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:
- 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)
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
- 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
rrCLL Cohort
rrMM Cohort
rrDLBCL 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.
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.
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.