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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

  Show 23 Study Locations
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