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

NCT02684617 | Terminated Phase 1 Results FDA Drug

• 3 other identifiers: 3475-155MK-3475-155KEYNOTE-155
• Study Type: interventional
• Target: 75
• Locations: 0 countries
• Sites: N/A

Brief 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).

Conditions

rrCLL; rrMM; rrDLBCL

Outcome Measures

Primary Outcomes (3)

• 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 (4)

• Objective Response Rate (ORR)

  Up to approximately 26 months

• Duration of Response (DOR)

  Up to approximately 26 months

• Progression-Free Survival (PFS)

  Up to approximately 26 months

• Overall Survival (OS)

  Up to approximately 44 months

Study Arms (3)

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

pembrolizumab BIOLOGICAL

200 mg administered as an intravenous (IV) infusion on Day 1 of infusion Cycles 1-35. Each cycle is 21 days.

Also known as: MK-3475, SCH 9000475, KEYTRUDA®

rrCLL Cohort; rrDLBCL Cohort; rrMM Cohort

dinaciclib DRUG

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.

Also known as: MK-7965

rrCLL Cohort; rrDLBCL Cohort; rrMM Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 34972202 DERIVED

Related Links

• Merck Oncology Clinical Trials Information

MeSH Terms

Interventions

pembrolizumab; dinaciclib

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2016
• First Posted: February 18, 2016
• Study Start: March 29, 2016
• Primary Completion: April 6, 2020
• Study Completion: April 6, 2020
• Last Updated: March 1, 2021
• Results First Posted: March 1, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share