Clinical Trials /

A Study of MGD013 in Patients With Unresectable or Metastatic Neoplasms

NCT03219268

Description:

The primary goal of this Phase 1 study is to characterize the safety and tolerability of MGD013 and establish the maximum tolerated dose (MTD) of MGD013. Pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD), and the anti-tumor activity of MGD013 will also be assessed.

Related Conditions:
  • Leukemia
  • Malignant Bone Marrow Neoplasm
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of MGD013 in Patients With Unresectable or Metastatic Neoplasms
  • Official Title: A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of MGD013, A Bispecific DART® Protein Binding PD-1 and LAG-3 in Patients With Unresectable or Metastatic Neoplasms

Clinical Trial IDs

  • ORG STUDY ID: CP-MGD013-01
  • NCT ID: NCT03219268

Conditions

  • Advanced Solid Tumors
  • Hematologic Neoplasms

Interventions

DrugSynonymsArms
MGD013MGD013
MGD013 in combination with margetuximabMGAH22MGD013 plus margetuximab

Purpose

The primary goal of this Phase 1 study is to characterize the safety and tolerability of MGD013 and establish the maximum tolerated dose (MTD) of MGD013. Pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD), and the anti-tumor activity of MGD013 will also be assessed.

Detailed Description

      This is a Phase 1, open-label, dose escalation and cohort expansion study designed to
      characterize the safety, tolerability, PK, PD, immunogenicity, and preliminary antitumor
      activity of MGD013 administered by IV infusion on every 2 weeks. The study consists of a Dose
      Escalation Phase to determine the MTD or maximum administered dose (MAD) of MGD013 if no MTD
      is defined, followed by a Cohort Expansion Phase to further define the safety and initial
      antitumor activity of MGD013 with the dose established in the Dose Escalation Phase.

      In the Dose Escalation Phase, MGD013 will be evaluated in sequential escalating flat doses in
      successive cohorts of 1 to 6 patients each. Upon completion of the Dose Escalation Phase, a
      Cohort Expansion Phase will be initiated at the MTD/MAD.

      Patients with unresectable, locally advanced or metastatic solid tumors of any histology will
      be enrolled in the Dose Escalation Phase. The Cohort Expansion Phase will be limited to
      selected cohorts of patients with unresectable, locally advanced or metastatic solid tumors
      or hematologic malignancies for whom there is no available therapy likely to confer clinical
      benefit.

      A separate cohort will evaluate the combination of MGD013 with margetuximab (anti-HER2
      monoclonal antibody) in approximately 12 patients with HER2-positive cancer.
    

Trial Arms

NameTypeDescriptionInterventions
MGD013ExperimentalMGD013 administered IV once every 2 weeks for up to 12 8-week cycles
  • MGD013
MGD013 plus margetuximabExperimentalMGD013 administered in combination with margetuximab IV once every 3 weeks for up to 35 3-week cycles
  • MGD013
  • MGD013 in combination with margetuximab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically proven, locally advanced unresectable or metastatic solid tumors (or
             hematologic malignancies, Cohort Expansion only) for whom no approved therapy with
             demonstrated clinical benefit is available or standard treatment was declined.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Life expectancy ≥ 12 weeks

          -  Measurable disease

          -  Tissue specimen available for retrospective analysis of PD-1, PD-L1, LAG-3, and MHC-II
             expression

          -  Acceptable laboratory parameters

        HER2+ Cohort:

        - Locally advanced or metastatic HER2+ locally advanced or metastatic solid tumors,
        regardless of organ of origin.

        i. The cancer must have progressed following standard therapy, or has progressed during or
        after HER2-directed therapy if approved and available for patients with HER2+ breast or
        gastric cancer.

        ii. History of HER2 positivity defined as 3+ by IHC or 2+ by IHC in combination with in
        situ hybridization (ISH) positivity most recent tumor biopsy.

        Exclusion Criteria:

          -  Symptomatic central nervous system (CNS) metastases or primary CNS lymphoma

          -  History of allogeneic bone marrow, stem-cell, or solid organ transplant

          -  History of known or suspected autoimmune disease with the specific exceptions of
             vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring systemic
             treatment (within the past 2 years), and patients with a history of Grave's disease
             that are now euthyroid clinically and by laboratory testing.

          -  Treatment with any systemic chemotherapy within 3 weeks prior to the initiation of
             study drug; treatment with biologics or investigational therapy within the 4 weeks
             prior to the initiation of study drug.

          -  Major surgery within 4 weeks prior to the initiation of study drug.

          -  Prior treatment with combination of monoclonal antibodies against PD-1 and LAG-3
             (Cohort Expansion only).

          -  Treatment with radiation therapy within 2 weeks prior to the initiation of study drug.

          -  Clinically significant cardiovascular disease.

          -  QTcF prolongation > 480 milliseconds

          -  HER2+ cohort: left ventricular ejection fraction less than 50%

          -  Clinically significant pulmonary compromise, including a requirement for supplemental
             oxygen use to maintain adequate oxygenation.

          -  Active pneumonitis or history of non-infectious pneumonitis.

          -  Clinically significant gastrointestinal disorders.

          -  Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral
             treatment within 7 days prior to the initiation of study drug.

          -  Known history of positive testing for human immunodeficiency virus or history of
             acquired immune deficiency syndrome.

          -  Known history of hepatitis B (except in hepatocellular carcinoma) or hepatitis C
             infection or known positive test for hepatitis B surface antigen, hepatitis B core
             antigen, or hepatitis C polymerase chain reaction (PCR)

          -  Vaccination with any live virus vaccine within 4 weeks prior to the initiation of
             study drug administration. Inactivated annual influenza vaccination is allowed

          -  Dementia or altered mental status that would preclude understanding and rendering of
             informed consent
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03
Time Frame:24 months
Safety Issue:
Description:Safety Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit.

Secondary Outcome Measures

Measure:Area Under the Plasma Concentration versus Time Curve (AUC) of MGD013 and MGD013 plus margetuximab
Time Frame:24 months
Safety Issue:
Description:AUC
Measure:Maximum Plasma Concentration (Cmax) of MGD013 and MGD013 plus margetuximab
Time Frame:24 months
Safety Issue:
Description:Cmax
Measure:Time to reach maximum (peak) plasma concentration (Tmax) of MGD013 and MGD013 plus margetuximab
Time Frame:24 months
Safety Issue:
Description:Tmax
Measure:Trough plasma concentration (Ctrough) of MGD013 and MGD013 plus margetuximab
Time Frame:24 months
Safety Issue:
Description:Ctrough
Measure:Total body clearance of the drug from plasma (CL) of MGD013 and MGD013 plus margetuximab
Time Frame:24 months
Safety Issue:
Description:CL
Measure:Apparent volume of distribution at steady state (Vss) of MGD013 and MGD013 plus margetuximab
Time Frame:24 months
Safety Issue:
Description:Vss
Measure:Terminal half-life (t1/2) of MGD013 and MGD013 plus margetuximab
Time Frame:24 months
Safety Issue:
Description:t1/2
Measure:Percent of patients with anti-drug antibody
Time Frame:24 months
Safety Issue:
Description:immunogenicity
Measure:Efficacy: Preliminary anti-tumor activity of MGD013 and MGD013 plus margetuximab
Time Frame:36 months
Safety Issue:
Description:Preliminary anti-tumor activity of MGD013 and MGD013 plus margetuximab

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:MacroGenics

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