Clinical Trials /

Study of MK-4280 as Monotherapy and in Combination With Pembrolizumab (MK-3475) With or Without Chemotherapy AND MK-4280A as Monotherapy in Adults With Advanced Solid Tumors (MK-4280-001)

NCT02720068

Description:

This is a safety and pharmacokinetics study of MK-4280 as monotherapy and in combination with pembrolizumab (MK-3475) AND MK-4280A as monotherapy in adults with metastatic solid tumors for which there is no available therapy which may convey clinical benefit. Part A of this study is a dose escalation design in which participants receive MK-4280 as monotherapy or MK-4280 in combination with pembrolizumab. Part B is a dose confirmation design to estimate the recommended Phase 2 dose (RPTD), as determined by dose-limiting toxicity, for MK-4280 in combination with pembrolizumab in participants with advanced solid tumors. Part B will also assess the efficacy of MK-4280 as monotherapy and in combination with pembrolizumab with and without chemotherapy AND MK-4280A as monotherapy in expansion cohorts.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of MK-4280 as Monotherapy and in Combination With Pembrolizumab (MK-3475) With or Without Chemotherapy AND MK-4280A as Monotherapy in Adults With Advanced Solid Tumors (MK-4280-001)
  • Official Title: A Phase 1 Trial of MK-4280 as Monotherapy and in Combination With Pembrolizumab With or Without Chemotherapy in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 4280-001
  • SECONDARY ID: 2017-001464-38
  • SECONDARY ID: MK-4280-001
  • SECONDARY ID: 183971
  • NCT ID: NCT02720068

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
MK-4280Part A: MK-4280 Dose A
PembrolizumabMK-3475, KEYTRUDA®Part A: MK-4280 Dose A+Pembro
OxaliplatinELOXATIN®Part B: MK-4280 Dose G+Pembro+mFOLFOX7
IrinotecanCAMPTOSAR®Part B: MK-4280 Dose G+Pembro+FOLFIRI
Leucovorin (Calcium Folinate)WELLCOVORIN®Part B: MK-4280 Dose G+Pembro+mFOLFOX7
Fluorouracil [5-FU]ADRUCIL®Part B: MK-4280 Dose G+Pembro+mFOLFOX7
MK-4280APart B: MK-4280A

Purpose

This is a safety and pharmacokinetics study of MK-4280 as monotherapy and in combination with pembrolizumab (MK-3475) AND MK-4280A as monotherapy in adults with metastatic solid tumors for which there is no available therapy which may convey clinical benefit. Part A of this study is a dose escalation design in which participants receive MK-4280 as monotherapy or MK-4280 in combination with pembrolizumab. Part B is a dose confirmation design to estimate the recommended Phase 2 dose (RPTD), as determined by dose-limiting toxicity, for MK-4280 in combination with pembrolizumab in participants with advanced solid tumors. Part B will also assess the efficacy of MK-4280 as monotherapy and in combination with pembrolizumab with and without chemotherapy AND MK-4280A as monotherapy in expansion cohorts.

Trial Arms

NameTypeDescriptionInterventions
Part A: MK-4280 Dose AExperimentalParticipants receive MK-4280 Dose A intravenous (IV) infusion on Day 1 of each 21-day cycle.
  • MK-4280
Part A: MK-4280 Dose BExperimentalParticipants receive MK-4280 Dose B IV infusion on Day 1 of each 21-day cycle.
  • MK-4280
Part A: MK-4280 Dose CExperimentalParticipants receive MK-4280 Dose C IV infusion on Day 1 of each 21-day cycle.
  • MK-4280
Part A: MK-4280 Dose DExperimentalParticipants receive MK-4280 Dose D IV infusion on Day 1 of each 21-day cycle.
  • MK-4280
Part A: MK-4280 Dose EExperimentalParticipants receive MK-4280 Dose E IV infusion on Day 1 of each 21-day cycle.
  • MK-4280
Part A: MK-4280 Dose A+PembroExperimentalParticipants receive MK-4280 Dose A IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab IV infusion administered sequentially on Day 1 of each 21-day cycle.
  • MK-4280
  • Pembrolizumab
Part A: MK-4280 Dose B+PembroExperimentalParticipants receive MK-4280 Dose B IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab IV infusion administered sequentially on Day 1 of each 21-day cycle.
  • MK-4280
  • Pembrolizumab
Part A: MK-4280 Dose C+PembroExperimentalParticipants receive MK-4280 Dose C IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab IV infusion administered sequentially on Day 1 of each 21-day cycle.
  • MK-4280
  • Pembrolizumab
Part A: MK-4280 Dose D+PembroExperimentalParticipants receive MK-4280 Dose D IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab IV infusion administered sequentially on Day 1 of each 21-day cycle.
  • MK-4280
  • Pembrolizumab
Part A: MK-4280 Dose E+PembroExperimentalParticipants receive MK-4280 Dose E IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab IV infusion administered sequentially on Day 1 of each 21-day cycle.
  • MK-4280
  • Pembrolizumab
Part B: MK-4280 Monotherapy DoseExperimentalParticipants receive MK-4280 monotherapy dose IV infusion on Day 1 of each 21-day cycle.
  • MK-4280
Part B: MK-4280 Dose F+PembroExperimentalParticipants receive MK-4280 Dose F IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab IV infusion administered sequentially on Day 1 of each 21-day cycle.
  • MK-4280
  • Pembrolizumab
Part B: MK-4280 Dose G+PembroExperimentalParticipants receive MK-4280 Dose G IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab IV infusion administered sequentially on Day 1 of each 21-day cycle.
  • MK-4280
  • Pembrolizumab
Part B: MK-4280 Dose H+PembroExperimentalParticipants receive MK-4280 Dose H IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab IV infusion administered sequentially on Day 1 of each 21-day cycle.
  • MK-4280
  • Pembrolizumab
Part B: MK-4280 Dose G+Pembro+mFOLFOX7ExperimentalParticipants receive MK-4280 Dose G IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab IV infusion administered sequentially on Day 1 of each 21-day cycle PLUS mFOLFOX7 (oxaliplatin 85 mg/m^2 IV, leucovorin [calcium folinate] 400 mg/m^2 IV and fluorouracil [5-FU] 2400 mg/m^2 IV over 46 to 48 hours every 2 weeks [Q2W]).
  • MK-4280
  • Pembrolizumab
  • Oxaliplatin
  • Leucovorin (Calcium Folinate)
  • Fluorouracil [5-FU]
Part B: MK-4280 Dose G+Pembro+FOLFIRIExperimentalParticipants receive MK-4280 Dose G IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab IV administered sequentially on Day 1 of each 21-day cycle PLUS FOLFIRI (irinotecan 180 mg/m^2 IV, leucovorin [calcium folinate] 400 mg/m^2 IV and 5-FU 2400 mg/m^2 IV over 46 to 48 hours Q2W).
  • MK-4280
  • Pembrolizumab
  • Irinotecan
  • Leucovorin (Calcium Folinate)
  • Fluorouracil [5-FU]
Part B: MK-4280AExperimentalParticipants receive MK-4280A (MK-4280 and pembrolizumab administered as a co-formulation) IV infusion on Day 1 of each 21-day cycle.
  • MK-4280A

Eligibility Criteria

        Inclusion Criteria:

          -  Part A and Part B: Has histologically or cytologically-confirmed metastatic solid
             tumor.

          -  Has measurable disease by immune-related Response Evaluation Criteria in Solid Tumors
             (irRECIST) 1.1 criteria.

          -  Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale.

          -  Demonstrates adequate organ function

          -  If female of child-bearing potential, is willing to use an adequate method of
             contraception for the course of the study through 120 days after the last dose of
             study drug.

          -  If male with a female partner(s) of child-bearing potential, must agree to use an
             adequate method of contraception starting with the first dose of study drug through
             120 days after the last dose of study drug. Males with pregnant partners must agree to
             use a condom; no additional method of contraception is required for the pregnant
             partner.

        Exclusion Criteria:

          -  Has had chemotherapy, radiation or biological cancer therapy within 4 weeks prior to
             the first dose of study drug, or has not recovered to Common Terminology Criteria for
             Adverse Events (CTCAE) Grade 0 or 1 from the AEs due to cancer therapeutics
             administered more than 4 weeks earlier (this includes participants with previous
             immunomodulatory therapy with residual immune-related [ir]AEs).

          -  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 4 weeks of the first dose of study drug.

          -  Has received previous treatment with another agent targeting the lymphocyte-activation
             gene 3 (LAG-3) receptor.

          -  Has received previous treatment with an immunomodulatory therapy (e.g. anti-programmed
             cell death-1/anti-programmed cell death-ligand 1 [anti-PD-1/anti-PD-L1] or cytotoxic
             T-lymphocyte-associated protein 4 [CTLA 4] agent) and was discontinued from that
             therapy due to a Grade 3 or higher irAE.

          -  Is expected to require any other form of antineoplastic therapy while on study.

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             in excess of replacement doses, or on any other form of immunosuppressive medication.

          -  Has a history of a previous, additional malignancy, unless potentially curative
             treatment has been completed, with no evidence of malignancy for 5 years. Time frame
             exceptions include successful definitive resection of basal cell carcinoma of the
             skin, superficial bladder cancer or in situ cervical cancer, or other in situ cancers.

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis.

          -  Has had a severe hypersensitivity reaction to treatment with another monoclonal
             antibody.

          -  Has an active autoimmune disease or a documented history of autoimmune disease, except
             vitiligo or resolved childhood asthma/atopy.

          -  Has an active infection requiring therapy.

          -  Has history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis.

          -  Has had a prior stem cell or bone marrow transplant.

          -  Has a known history of or screens positive for Human Immunodeficiency Virus (HIV),
             active chronic or acute Hepatitis B or Hepatitis C.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the study.

          -  Is a regular user as determined by investigator judgment (including "recreational
             use") of any illicit drugs or has a recent history (within the last year) of substance
             abuse (including alcohol), at the time of signing informed consent.

          -  Has symptomatic ascites or pleural effusion. A participant who is clinically stable
             following treatment for these conditions (including therapeutic thoraco- or
             paracentesis) is eligible.

          -  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 drug.

          -  Has clinically significant heart disease that affects normal activities.

          -  Has had major surgery in the past 4 weeks.

          -  Has received a live-virus vaccine within 30 days of planned start of study drug.
             Seasonal flu vaccines that do not contain live virus are permitted.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants Who Experience a Dose-Limiting Toxicity (DLT)
Time Frame:Up to approximately 2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective Response Rate (ORR) as Determined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as Assessed by Investigator Review of MK-4280 in Combination With Pembrolizumab
Time Frame:Up to approximately 2 years
Safety Issue:
Description:
Measure:ORR as Determined by RECIST 1.1 as Assessed by Investigator Review of Two Doses of MK-4280 in Combination With Pembrolizumab for Participants with Advanced Solid Tumors in Cohort E
Time Frame:Up to approximately 2 years
Safety Issue:
Description:
Measure:ORR as Determined by RECIST 1.1 as Assessed by Investigator Review of MK-4280 in Combination With Pembrolizumab and mFOLFOX7 for Participants with Advanced Solid Tumors in Cohort B
Time Frame:Up to approximately 2 years
Safety Issue:
Description:
Measure:ORR as Determined by RECIST 1.1 as Assessed by Investigator Review of MK-4280 in Combination With Pembrolizumab and FOLFIRI for Participants with Advanced Solid Tumors in Cohort B
Time Frame:Up to approximately 2 years
Safety Issue:
Description:
Measure:Serum Concentration of MK-4280 When Administered as Monotherapy
Time Frame:At designated time points (Up to approximately 2 years)
Safety Issue:
Description:
Measure:Serum Concentration of MK-4280 When Administered in Combination With Pembrolizumab
Time Frame:At designated time points (Up to approximately 2 years)
Safety Issue:
Description:
Measure:Serum Concentration of MK-4280 When Administered in Combination With Pembrolizumab and mFOLFOX7
Time Frame:At designated time points (Up to approximately 2 years)
Safety Issue:
Description:
Measure:Serum Concentration of MK-4280 When Administered in Combination With Pembrolizumab and FOLFIRI
Time Frame:At designated time points (Up to approximately 2 years)
Safety Issue:
Description:
Measure:At designated time points (Up to approximately 2 years)
Time Frame:At designated time points (Up to approximately 2 years)
Safety Issue:
Description:
Measure:Serum Concentration of Pembrolizumab When Administered in Combination With MK-4280 and mFOLFOX7
Time Frame:At designated time points (Up to approximately 2 years)
Safety Issue:
Description:
Measure:Serum Concentration of Pembrolizumab When Administered in Combination With MK-4280 and FOLFIRI
Time Frame:At designated time points (Up to approximately 2 years)
Safety Issue:
Description:
Measure:Serum Concentration of MK-4280 When Administered as a Co-Formulation With Pembrolizumab (MK-4280A)
Time Frame:At designated time points (Up to approximately 2 years)
Safety Issue:
Description:
Measure:Serum Concentration of MK-4280 When Administered Sequentially With Pembrolizumab
Time Frame:At designated time points (Up to approximately 2 years)
Safety Issue:
Description:
Measure:Serum Concentration of Pembrolizumab When Administered as a Co-Formulation With MK-4280 (MK-4280A)
Time Frame:At designated time points (Up to approximately 2 years)
Safety Issue:
Description:
Measure:Serum Concentration of Pembrolizumab When Administered Sequentially With MK-4280
Time Frame:At designated time points (Up to approximately 2 years)
Safety Issue:
Description:

Details

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

Trial Keywords

  • PD1
  • PD-1
  • PDL1
  • PD-L1

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