Clinical Trials /

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)

NCT03598608

Description:

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.

Related Conditions:
  • Classical Hodgkin Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Indolent Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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: 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

Clinical Trial IDs

  • ORG STUDY ID: 4280-003
  • SECONDARY ID: MK-4280-003
  • SECONDARY ID: 2018-001461-16
  • NCT ID: NCT03598608

Conditions

  • Hodgkin Disease
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell

Interventions

DrugSynonymsArms
pembrolizumabKEYTRUDA®, MK-3475Part A: MK-4280 Dose A+pembrolizumab
MK-4280Part A: MK-4280 Dose A+pembrolizumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Part A: MK-4280 Dose A+pembrolizumabExperimentalParticipants 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.
  • pembrolizumab
  • MK-4280
Part A: MK-4280 Dose B+pembrolizumabExperimentalParticipants 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.
  • pembrolizumab
  • MK-4280
Part A: MK-4280 Dose C+PembrolizumabExperimentalParticipants 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.
  • pembrolizumab
  • MK-4280
Part B: cHLExperimentalParticipants 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.
  • pembrolizumab
  • MK-4280
Part B: DLBCLExperimentalParticipants 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.
  • pembrolizumab
  • MK-4280
Part B: iNHLExperimentalParticipants 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.
  • pembrolizumab
  • MK-4280

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants Experiencing a Dose-limiting Toxicity (DLT)
Time Frame:Cycle 1 (up to 21 days)
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Up to approximately 24 months
Safety Issue:
Description: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.
Measure:Serum Concentration of MK-4280
Time Frame:At designated time points (Up to approximately 25 months)
Safety Issue:
Description: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.
Measure:Serum Concentration of Pembrolizumab
Time Frame:At designated time points (Up to approximately 25 months)
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • programmed cell death 1 (PD-1, PD1)
  • programmed cell death ligand 1 (PD-L1, PDL1)
  • programmed cell death ligand 2 (PD-L2, PDL2)

Last Updated

January 17, 2020