SHS_492327 PAGJ CMER 16040

Phase Ib Trial of Pembrolizumab (MK-3475) in Combination With Dinaciclib (MK-7965) in Subjects With Hematologic Malignancies (KEYNOTE-155)

This is a non-randomized, open-label study evaluating 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) in up to 138 participants from multiple sites. During an initial Dose Evaluation phase (first 2 cycles) to determine Dose Limiting Toxicities (DLTs), dose combinations of pembrolizumab 200 mg + dinaciclib 7 mg/m^2, pembrolizumab 200 mg + dinaciclib 10 mg/m^2, and pembrolizumab 200 mg + dinaciclib 14 mg/m^2 will be evaluated. Following safety review of the Dose Evaluation Phase, approximately 30 participants each will be enrolled in rrCLL, rrMM, or DLBCL cohorts during the Signal Detection phase. For each disease type objective response rate (ORR) will be determined by disease specific criteria.

Select Inclusion Criteria:

Females must not be pregnant
Women of childbearing potential and male participants must agree to use adequate contraception up to 120 days after study therapy
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Must be able to provide biopsy specimens obtained ≤3 months for biomarker analysis

CLL Participants:
Confirmed diagnosis of CLL defined by 2008 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
received one prior therapy for CLL
Must meet one or more of the consensus criteria for initiating treatment

MM Participants:
Confirmed diagnosis of active MM
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)
Failed prior anti-myeloma treatments that have included an immunomodulatory drug (IMiD) (pomalidomide, lenalidomide, or thalidomide) AND proteasome inhibitor (bortezomib or carfilzomib) alone or in combination.

DLBCL Participants:
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
Measurable disease (≥1 lesion that is >15 mm in the longest diameter and by >10 mm in the short axis)

Select Exclusion Criteria:

Treated with a cytochrome P450 3A4 (CYP3A4) strong inhibitor or inducer within 7 days of enrollment
Treated with anti-cancer therapy or thoracic radiation therapy within 14 days
Clinically active CNS involvement
Known history of immunosuppression or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days
Prior anti-cancer monoclonal antibody within 4 weeks of Study Day 1or who has not recovered from adverse events due to agents administered >4 weeks earlier
undergone prior allogeneic hematopoetic stem cell transplantation within the last 5 years
Known additional malignancy that is progressing or requires active treatment
Active autoimmune disease that has required systemic treatment in past 2 years
Received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody
Previously treated with a CDK inhibitor
Known Human Immunodeficiency Virus (HIV), or active Hepatitis B (HBV), or C (HCV) infection
Received a live vaccine within 30 days prior to the first dose of trial treatment
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)
Participants with primary mediastinal B-cell lymphoma (PMBCL)
Phase Ib
John Pagel, M.D.
Ngan Trinh
  • Swedish Medical Center