Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

Study of Pembrolizumab (MK-3475) in Combination With Dinaciclib (MK-7965) in Hematologic Malignancies (MK-3475-155)

Protocol: OSU-16014

Full Title

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

Purpose

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 followed by dinaciclib 7

mg/m^2, pembrolizumab 200 mg followed by dinaciclib 10 mg/m^2, and pembrolizumab 200 mg

followed by 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.

Are you eligible?

Inclusion Criteria:

Females must not be pregnant (negative urine or serum human chorionic gonadotropin

test within 72 hours of study start)

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:

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

MM 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 or carfilzomib) alone or in combination.

DLBCL 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 and 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 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 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

Has been previously treated with a CDK inhibitor

Has known Human Immunodeficiency Virus (HIV), or active Hepatitis B (HBV), or C (HCV)

infection

Has 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)

Has a history of (non-infectious) pneumonitis that required steroids or current

pneumonitis

Leukemia Chronic Lymphocytic Leukemia Lymphoma Non-Hodgkin’s Lymphoma (B- & T-Cell) Multiple Myeloma