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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.

Tracking Information
First Submitted Date  ICMJE July 16, 2018
First Posted Date  ICMJE July 25, 2018
Last Update Posted Date August 21, 2019
Actual Study Start Date  ICMJE October 17, 2018
Estimated Primary Completion Date July 18, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 3, 2019)
  • 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
  • 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
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: July 16, 2018)
  • 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 except platelet count decreased
    • gr 4 platelet count decreased of any duration
    • gr 3 platelet count decreased 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
  • 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 25 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
  • 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
Change History Complete list of historical versions of study NCT03598608 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 3, 2019)
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2018)
  • 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.
  • Serum Concentration of MK-4280 [ Time Frame: At designated time points (Up to approximately 25 months) ]
    Blood samples are to 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 drawn at the 30-day follow-up visit.
  • Serum Concentration of Pembrolizumab [ Time Frame: At designated time points (Up to approximately 25 months) ]
    Blood samples are to 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 drawn at the 30-day follow-up visit.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hodgkin Disease
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Biological: pembrolizumab
    • Biological: MK-4280
  • 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.
    Interventions:
    • Biological: pembrolizumab
    • Biological: MK-4280
  • 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.
    Interventions:
    • Biological: pembrolizumab
    • Biological: MK-4280
  • 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.
    Interventions:
    • Biological: pembrolizumab
    • Biological: MK-4280
  • 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.
    Interventions:
    • Biological: pembrolizumab
    • Biological: MK-4280
  • 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.
    Interventions:
    • Biological: pembrolizumab
    • Biological: MK-4280
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 16, 2018)
134
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 18, 2025
Estimated Primary Completion Date July 18, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com
Listed Location Countries  ICMJE Australia,   Canada,   Germany,   Israel,   Italy,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03598608
Other Study ID Numbers  ICMJE 4280-003
MK-4280-003 ( Other Identifier: Merck Protocol Number )
2018-001461-16 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP