Study of Pembrolizumab (MK-3475) in Combination With Dinaciclib (MK-7965) in Hematologic Malignancies (MK-3475-155/KEYNOTE-155)
Condition: rrCLL; rrMM; rrDLBCL
MeSH terms: Hematologic Neoplasms
Intervention: pembrolizumab; dinaciclib
Intervention description: 200 mg administered as an intravenous (IV) infusion on Day 1 of infusion Cycles 1-35. Each cycle is 21 days.; dinaciclib 7 mg/m^2 administered as an IV infusion on Day 1 of infusion Cycle 1, dinaciclib 10 mg/m^2 administered as an IV infusion on Day 8 of infusion Cycle 1, dinaciclib 14 mg/m^2 administered as an IV infusion on Days 1 and 8 of infusion Cycles 2-35. Each cycle is 21 days.
Intervention MeSH terms: Pembrolizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 75.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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).
    

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