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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02684617




Registration number
NCT02684617
Ethics application status
Date submitted
12/02/2016
Date registered
12/02/2016
Date last updated
28/02/2019

Titles & IDs
Public title
Study of Pembrolizumab (MK-3475) in Combination With Dinaciclib (MK-7965) in Hematologic Malignancies (MK-3475-155)
Scientific title
Phase Ib Trial of Pembrolizumab (MK-3475) in Combination With Dinaciclib (MK-7965) in Subjects With Hematologic Malignancies (KEYNOTE-155).
Secondary ID [1] 0 0
MK-3475-155
Secondary ID [2] 0 0
3475-155
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
rrCLL 0 0
rrMM 0 0
rrDLBCL 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - pembrolizumab
Treatment: Drugs - dinaciclib

Experimental: Pembrolizumab and Dinaciclib - During the Dose Evaluation phase of the study, 12 participants will receive an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7mg/m^2 on Cycle 1 Day 1 and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants will then receive an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14mg/m^2 on Day 1 and infusion of dinaciclib 14mg/m^2 alone on Day 8 on Cycles 2 through 35. The study design will be revised based on the number of DLTs in Cycle 1 and Cycle 2. If =4 DLTs occur, 30 participants per disease type will be enrolled in the Signal Detection Phase. If >5 DLTs occur, a lower dose will be evaluated in up to 24 additional participants.


Other interventions: pembrolizumab
200 mg administered as an intravenous (IV) infusion on Day 1 of infusion Cycles 1-35

Treatment: Drugs: dinaciclib
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

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with Dose Limiting Toxicity (DLT)
Timepoint [1] 0 0
Cycles 1 and 2 (up to 42 days)
Primary outcome [2] 0 0
Number of participants with Adverse Events (AEs)
Timepoint [2] 0 0
From time of first dose until the end of follow-up (up to 26 months)
Primary outcome [3] 0 0
Number of participants discontinuing study drug due to AEs
Timepoint [3] 0 0
From time of first dose until the end of follow-up (up to 26 months)
Secondary outcome [1] 0 0
Objective Response Rate (ORR) (disease specific)
Timepoint [1] 0 0
From time of screening until end of follow-up (up to 26 months)

Eligibility
Key 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

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, carfilzomib, or ixazomib) 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 or by
>10 mm in the short axis)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 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

- 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)

- Participants with CLL or DLBCL who have Richter's Transformation

- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Merck Sharp & Dohme - North Ryde
Recruitment postcode(s) [1] 0 0
- North Ryde
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
New Jersey
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
United States of America
State/province [9] 0 0
Wisconsin

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.

The rrMM cohort was closed to enrollment on 07-AUG-2017 due to lack of efficacy.
Trial website
https://clinicaltrials.gov/show/NCT02684617
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02684617