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Study to Evaluate the Safety and Efficacy of a Combination of MK-4280 and Pembrolizumab (MK-3475) in Participants With Hematologic Malignancies (MK-4280-003)

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ClinicalTrials.gov Identifier: NCT03598608
Recruitment Status : Recruiting
First Posted : July 25, 2018
Last Update Posted : August 21, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:

This study will evaluate the safety and efficacy of MK-4280 in combination with pembrolizumab (MK-3475) in participants with hematological malignancies:

  • classical Hodgkin lymphoma (cHL)
  • diffuse large B-cell lymphoma (DLBCL)
  • indolent non-Hodgkin lymphoma (iNHL) The study will have 2 phases: a safety lead-in and an efficacy expansion phase. The recommended Phase 2 dose (RPTD) will be determined in the safety lead-in phase by evaluating dose-limiting toxicities.

Condition or disease Intervention/treatment Phase
Hodgkin Disease Lymphoma, Non-Hodgkin Lymphoma, B-Cell Biological: pembrolizumab Biological: MK-4280 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 134 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/Phase 2 Clinical Study to Evaluate the Safety and Efficacy of a Combination of MK-4280 and Pembrolizumab (MK-3475) in Participants With Hematologic Malignancies
Actual Study Start Date : October 17, 2018
Estimated Primary Completion Date : July 18, 2025
Estimated Study Completion Date : December 18, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part A: MK-4280 Dose A+pembrolizumab
Participants receive 200 mg pembrolizumab by intravenous (IV) infusion followed by MK-4280 Dose A by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles.
Biological: pembrolizumab
Administered as an IV infusion every 3 weeks (Q3W)
Other Names:
  • KEYTRUDA®
  • MK-3475

Biological: MK-4280
Administered as an IV infusion Q3W

Experimental: Part A: MK-4280 Dose B+pembrolizumab
Participants receive 200 mg pembrolizumab by IV infusion followed by MK-4280 Dose B by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles.
Biological: pembrolizumab
Administered as an IV infusion every 3 weeks (Q3W)
Other Names:
  • KEYTRUDA®
  • MK-3475

Biological: MK-4280
Administered as an IV infusion Q3W

Experimental: Part A: MK-4280 Dose C+Pembrolizumab
Participants receive 200 mg pembrolizumab by IV infusion followed by MK-4280 Dose C by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles.
Biological: pembrolizumab
Administered as an IV infusion every 3 weeks (Q3W)
Other Names:
  • KEYTRUDA®
  • MK-3475

Biological: MK-4280
Administered as an IV infusion Q3W

Experimental: Part B: cHL
Participants with cHL receive 200 mg pembrolizumab by IV infusion followed by the RPTD of MK-4280 by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles.
Biological: pembrolizumab
Administered as an IV infusion every 3 weeks (Q3W)
Other Names:
  • KEYTRUDA®
  • MK-3475

Biological: MK-4280
Administered as an IV infusion Q3W

Experimental: Part B: DLBCL
Participants with DLBCL receive 200 mg pembrolizumab by IV infusion followed by the RPTD of MK-4280 by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles.
Biological: pembrolizumab
Administered as an IV infusion every 3 weeks (Q3W)
Other Names:
  • KEYTRUDA®
  • MK-3475

Biological: MK-4280
Administered as an IV infusion Q3W

Experimental: Part B: iNHL
Participants with iNHL receive 200 mg pembrolizumab by IV infusion followed by the RPTD of MK-4280 by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles.
Biological: pembrolizumab
Administered as an IV infusion every 3 weeks (Q3W)
Other Names:
  • KEYTRUDA®
  • MK-3475

Biological: MK-4280
Administered as an IV infusion Q3W




Primary Outcome Measures :
  1. Percentage of Participants Experiencing a Dose-limiting Toxicity (DLT) [ Time Frame: Cycle 1 (up to 21 days) ]

    Percentage of participants experiencing a DLT defined by the National Cancer Institute Common Terminology for Adverse Events version 4.0 as:

    • grade (gr) 4 non-hematologic toxicity (not laboratory)
    • gr 4 hematologic toxicity lasting >7 days OR gr 4 platelet count decreased of any duration OR gr 3 platelet count decreased if associated with bleeding
    • any gr 3 non-hematologic toxicity (not laboratory) with the exception of gr 3 nausea, vomiting, or diarrhea (not be considered a DLT unless lasting >3 days despite optimal supportive care)
    • any gr 3 or 4 non-hematologic laboratory abnormality if medical intervention is required, or the abnormality leads to hospitalization, or the abnormality persists for >1 week
    • gr 3 or 4 febrile neutropenia
    • any treatment-related AE which caused participant to discontinue study intervention during the first cycle
    • gr 5 toxicity
    • any treatment-related toxicity which causes a >2-week delay in initiation of Cycle 2

  2. Percentage of Participants Experiencing an Adverse Event (AE) [ Time Frame: From time of signing informed consent form (ICF) until the end of follow-up (up to approximately 27 months) ]
    Percentage of participants experiencing an AE defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study treatment

  3. Percentage of Participants with Treatment Discontinuations Due to an AE [ Time Frame: From time of signing informed consent form (ICF) until the end of study treatment (up to approximately 24 months) ]
    Percentage of participants discontinuing study treatment due to an AE


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Up to approximately 24 months ]
    ORR is defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all evidence of disease) or a Partial Response (PR: ≥50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses; no increase should be observed in the size of other nodes, liver, or spleen; and splenic and hepatic nodules must regress by ≥50% in their SPD or, for single nodules, in the greatest transverse diameter) per lymphoma disease response criteria (Cheson et. al., 2007) as assessed by the investigator.

  2. Serum Concentration of MK-4280 [ Time Frame: At designated time points (Up to approximately 25 months) ]
    Blood samples will be collected at designated time points for the determination of the serum concentration of MK-4280. For Cycles 1 and 8: Day 1 at predose, end of infusion, and 4 hours postdose; Days 8 and 15 at any time. Cycles 2 through 7, Cycles 9 through 16 and every 4 cycles thereafter: Day 1 at predose. Blood samples will also be collected at the 30-day follow-up visit.

  3. Serum Concentration of Pembrolizumab [ Time Frame: At designated time points (Up to approximately 25 months) ]
    Blood samples will be collected at designated time points for the determination of the serum concentration of pembrolizumab. For Cycles 1 and 8: Day 1 at predose, end of infusion, and 4 hours postdose; Days 8 and 15 at any time. Cycles 2 through 7, Cycles 9 through 16 and every 4 cycles thereafter: Day 1 at predose. Blood samples will also be collected at the 30-day follow-up visit.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has measureable disease, defined as ≥1 lesion that can be accurately measured in 2 dimensions with diagnostic quality cross sectional anatomic imaging (computed tomography or magnetic resonance imaging). Minimum measurement must be >15 mm in the longest diameter or >10 mm in the short axis
  • Is able to provide a core or excisional tumor biopsy for biomarker analysis from an archival (within 3 months) or newly obtained biopsy at screening
  • Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)

Exclusion Criteria:

  • Has known clinically active central nervous system (CNS) involvement
  • Has received prior therapy with an anti-lymphocyte activation gene-3 (LAG-3) antibody
  • Has received chimeric antigen receptors (CAR)-T-cell therapy
  • Has received prior anticancer therapy or thoracic radiation therapy within 14 days before the first dose of study treatment
  • Has ≥Grade 2 non-hematological toxicities from prior therapy
  • Has had a prior anticancer monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤Grade 1 or at baseline) from AEs due to agents administered ≥4 weeks earlier
  • Has received a live vaccine within 30 days prior to first dose of study treatment
  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 28 days before study Day 1
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
  • Has a known additional malignancy that is progressing or requires active treatment with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
  • Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Has an active infection requiring intravenous systemic therapy
  • Has a known history of human immunodeficiency virus (HIV) infection
  • Has known, active hepatitis B or hepatitis C infection
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
  • Has had an allogeneic hematopoetic stem cell/solid organ transplantation within the last 5 years

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03598608


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

  Hide Study Locations
Locations
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United States, Arizona
Banner MD Anderson Cancer Center ( Site 0020) Recruiting
Gilbert, Arizona, United States, 85234
Contact: Study Coordinator    480-256-3425      
United States, California
City of Hope ( Site 0001) Recruiting
Duarte, California, United States, 91010
Contact: Study Coordinator    626-256-2405      
Ronald Reagan UCLA Medical Center (Radiological Sciences) ( Site 0007) Recruiting
Los Angeles, California, United States, 90095
Contact: Study Coordinator    310-582-4067      
Pacific Cancer Care ( Site 0006) Recruiting
Monterey, California, United States, 93940
Contact: Study Coordinator    831-375-4105      
University of California San Francisco ( Site 0023) Recruiting
San Francisco, California, United States, 94143
Contact: Study Coordinator    415-885-3882      
United States, Massachusetts
Dana Farber Cancer Institute ( Site 0002) Recruiting
Boston, Massachusetts, United States, 02215
Contact: Study Coordinator    617-632-2305      
United States, Texas
Texas Oncology-Austin Midtown ( Site 8002) Recruiting
Austin, Texas, United States, 78705
Contact: Study Coordinator    281-863-6701      
Australia, New South Wales
Concord Repatriation & General Hospital ( Site 0203) Recruiting
Concord, New South Wales, Australia, 2139
Contact: Study Coordinator    +61397677341      
Australia, Victoria
Monash Health ( Site 0201) Recruiting
Clayton, Victoria, Australia, 3168
Contact: Study Coordinator    +61395946666      
St Vincent s Hospital (Melbourne) Limited ( Site 0202) Recruiting
Fitzroy, Victoria, Australia, 3065
Contact: Study Coordinator    +61398593936      
Australia
Princess Alexandra Hospital ( Site 0204) Recruiting
Woollongabba, Australia, 4102
Contact: Study Coordinator    +61731766826      
Canada, British Columbia
BC Cancer ( Site 0107) Recruiting
Vancouver, British Columbia, Canada, V5Z 1L3
Contact: Study Coordinator    6048776000      
Canada, Manitoba
CancerCare Manitoba ( Site 0101) Recruiting
Winnipeg, Manitoba, Canada, R3E 0V9
Contact: Study Coordinator    2047874280      
Canada, Ontario
Princess Margaret Cancer Centre ( Site 0100) Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Study Coordinator    4169464501      
Canada, Quebec
Jewish General Hospital ( Site 0105) Recruiting
Montreal, Quebec, Canada, H3T 1E2
Contact: Study Coordinator    5143988307      
Germany
U. klinikum Koeln AOER ( Site 0326) Recruiting
Koeln, Germany, 50937
Contact: Study Coordinator    +4922147897657      
Israel
Rambam Medical Center ( Site 0382) Recruiting
Haifa, Israel, 3109601
Contact: Study Coordinator    +97247773109      
Hadassah Ein Karem Jerusalem ( Site 0383) Recruiting
Jerusalem, Israel, 9112001
Contact: Study Coordinator    +97226778243      
Chaim Sheba Medical Center. ( Site 0380) Recruiting
Ramat Gan, Israel, 5262001
Contact: Study Coordinator    +97235302588      
Sourasky Medical Center ( Site 0381) Recruiting
Tel Aviv, Israel, 6423906
Contact: Study Coordinator    +97236973782      
Italy
A.O. Universitaria Policlinico S. Orsola-Malpighi ( Site 0351) Recruiting
Bologna, Italy, 40138
Contact: Study Coordinator    +390516363680      
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori ( Site 0354) Recruiting
Meldola, Italy, 47014
Contact: Study Coordinator    +390543739290      
Istituto Clinico Humanitas Research Hospital ( Site 0352) Recruiting
Rozzano, Italy, 20089
Contact: Study Coordinator    +390282244080      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03598608     History of Changes
Other Study ID Numbers: 4280-003
MK-4280-003 ( Other Identifier: Merck Protocol Number )
2018-001461-16 ( EudraCT Number )
First Posted: July 25, 2018    Key Record Dates
Last Update Posted: August 21, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme Corp.:
programmed cell death 1 (PD-1, PD1)
programmed cell death ligand 1 (PD-L1, PDL1)
programmed cell death ligand 2 (PD-L2, PDL2)
Additional relevant MeSH terms:
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Lymphoma
Hodgkin Disease
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents