Study of Pembrolizumab (MK-3475) in Combination With Dina... | NCT02684617

NCT02684617

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
MK-3475-155	Other Identifier	Merck Protocol Number
KEYNOTE-155	Other Identifier	Merck

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
rrCLL Cohort	Experimental	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.	Biological: pembrolizumab Drug: dinaciclib
rrMM Cohort	Experimental	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.	Biological: pembrolizumab Drug: dinaciclib
rrDLBCL Cohort	Experimental	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.	Biological: pembrolizumab Drug: dinaciclib

Interventions

Name	Type	Description	Arm Group Labels	Other Names
pembrolizumab	Biological	200 mg administered as an intravenous (IV) infusion on Day 1 of infusion Cycles 1-35. Each cycle is 21 days.	rrCLL Cohort rrDLBCL Cohort

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Dose Limiting Toxicity (DLT)	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.	Up to 42 days
Number of Participants Who Experienced an Adverse Event	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.	Up to approximately 582 days
Number of Participants Who Discontinued Treatment Due to an Adverse Event	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.	Up to 492 days

Secondary Outcomes

Measure	Description	Time Frame
Objective Response Rate (ORR)	ORR is defined in participants with CLL as the percentage of participants who have a confirmed Complete Response (CR) or Partial Response (PR) per the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines (2008) as assessed by the investigator; in participants with DLBCL as the above definition but per the Revised Response Criteria for Malignant Lymphoma (2007) as assessed by the investigator; and in participants with MM as the percentage of participants who have a confirmed Stringent Complete Response (sCR), CR, PR, or Very Good Partial Remission (VGPR) per the International Uniform Response Criteria for Multiple Myeloma (2006) as assessed by the investigator.

Eligibility Module

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

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

PubMed Identifier	Type	Citation	Retractions
34972202	Derived	Gregory GP, Kumar S, Wang D, Mahadevan D, Walker P, Wagner-Johnston N, Escobar C, Bannerji R, Bhutani D, Chang J, Hernandez-Ilizaliturri FJ, Klein A, Pagel JM, Rybka W, Yee AJ, Mohrbacher A, Huang M, Farooqui M, Marinello P, Quach H. Pembrolizumab plus dinaciclib in patients with hematologic malignancies: the phase 1b KEYNOTE-155 study. Blood Adv. 2022 Feb 22;6(4):1232-1242. doi: 10.1182/bloodadvances.2021005872.

Label	URL
Merck Oncology Clinical Trials Information	View source

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	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.
FG002	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.

ID	Title	Description
BG000	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.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	Number of Participants With Dose Limiting Toxicity (DLT)	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.	The analysis population included all participants who received ≥1 dose of study medication, and who did not discontinue within the first two 21-day cycles of treatment or who experienced a DLT prior to completing the first two cycles of treatment.	Posted		Count of Participants		Participants		Up to 42 days

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.

ID	Term
C582435	pembrolizumab
C553669	dinaciclib