Clinical Trials /

MGD019 DART® Protein in Unresectable/Metastatic Cancer



The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of MGD019.

Related Conditions:
  • Colorectal Carcinoma
  • Malignant Solid Tumor
Recruiting Status:



Phase 1

Trial Eligibility



  • Brief Title: MGD019 DART® Protein in Unresectable/Metastatic Cancer
  • Official Title: A Phase 1, First-in-Human, Open-Label, Dose Escalation and Cohort Expansion Study of MGD019, a Bispecific DART® Protein Binding PD-1 and CTLA-4 in Patients With Unresectable or Metastatic Neoplasms

Clinical Trial IDs

  • ORG STUDY ID: CP-MGD019-01
  • NCT ID: NCT03761017


  • Solid Tumor, Adult
  • Advanced Cancer
  • Squamous Cell Non Small Cell Lung Cancer
  • Colorectal Cancer




The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of MGD019.

Detailed Description

      This Phase 1, open-label study will characterize safety, dose-limiting toxicities (DLTs), and
      maximum tolerated/administered dose (MTD/MAD) of MGD019. Dose escalation will occur in a
      3+3+3 design in patients with advanced solid tumors of any histology. Once the MTD/MAD is
      determined, a Cohort Expansion Phase will be enrolled to further characterize safety and
      initial anti-tumor activity in patients with specific tumor types anticipated to be sensitive
      to dual checkpoint blockade.

Trial Arms

MGD019ExperimentalBispecific DART protein binding PD-1 and CTLA-4
  • MGD019

Eligibility Criteria

        Inclusion Criteria:

          -  Dose escalation: Patients with histologically proven, unresectable, locally advanced
             or metastatic solid tumors for whom no approved therapy with demonstrated clinical
             benefit is available or patients who are intolerant to standard therapy.

          -  Cohort Expansion Phase:

          -  Checkpoint inhibitor-naïve squamous cell NSCLC, including:

               1. Patients that have progressed during or following treatment with platinum-based
                  chemotherapy for advanced disease. Patients harboring an activating epidermal
                  growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK)
                  rearrangement must have progressed following at least one available EGFR or ALK
                  targeted therapy.

               2. Patients with previously untreated squamous cell NSCLC without activating
                  mutations for whom checkpoint inhibitor therapy is not approved or available.

          -  Advanced non-microsatellite instability-high colorectal cancer (CRC) with recurrence,
             progression, or intolerance to standard therapy consisting of at least 2 prior
             standard regimens. CRC harboring an activating EGFR mutation must have progressed
             during or following at least one available EGFR targeted therapy. Patients who are
             inappropriate candidates for or have refused treatment with these regimens are also
             eligible. Patients should have received no more than 4 prior lines of systemic

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

          -  Life expectancy ≥ 12 weeks.

          -  Measurable disease as per RECIST 1.1 for the purpose of response assessment must
             either (a) not reside in a field that has been subjected to prior radiotherapy or (b)
             have demonstrated clear evidence of radiographic progression since the completion of
             prior radiotherapy and prior to study enrollment.

          -  All patients must have an identified formalin-fixed, paraffin embedded (FFPE) tumor
             specimen (up to 20 slides or a block) for immunohistochemical evaluation of
             pharmacodynamic markers of interest.

          -  Acceptable laboratory parameters and adequate organ reserve.

        Exclusion Criteria:

          -  In patients who have previously received an immune checkpoint inhibitor (e.g.,
             anti-PD-L1, anti-PD-1, anti-CTLA-4), toxicities related to the checkpoint inhibitor
             must have resolved to ≤ Grade 1 or baseline. Patients with well controlled immune
             endocrinopathies secondary to prior checkpoint therapy are eligible.

          -  Patients with symptomatic CNS metastases. Patients with history of prior CNS
             metastasis must have been treated, must be asymptomatic, and must not have concurrent
             treatment for the CNS disease, progression of CNS metastases on magnetic resonance
             imaging (MRI) or computed tomography (CT) for at least 14 days after last day of prior
             therapy for the CNS metastases, or concurrent leptomeningeal disease or cord

          -  Patients who sustained the following Grade 3 immune checkpoint inhibitor related AEs
             are ineligible: Ocular AE, changes in liver function tests that met the criteria for
             Hy's law (> 3 × ULN of either ALT or AST with concurrent > 2 × ULN of total bilirubin
             and without alternate etiology), neurologic toxicity, colitis, renal toxicity,

          -  Patients who have received prior therapy with a combination of monoclonal antibodies
             against PD-1/PD-L1 and CTLA-4 will be excluded in the Cohort Expansion.

          -  Patients with any history of known or suspected autoimmune disease with certain

          -  History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation.

          -  History of trauma, major surgical procedure, systemic antineoplastic therapy, or
             investigational therapy within the 4 weeks prior to initiation of study drug

          -  Treatment with radiation therapy within 2 weeks prior to initiation of study drug
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
Time Frame:30 days after last dose
Safety Issue:
Description: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

Time Frame:up to 108 weeks
Safety Issue:
Description:Maximum Plasma Concentration of MGD019
Time Frame:up to 108 weeks
Safety Issue:
Description:Time to reach maximum (peak) plasma concentration of MGD019
Time Frame:up to 108 weeks
Safety Issue:
Description:Area Under the Plasma Concentration versus Time Curve of MGD019
Time Frame:up to 108 weeks
Safety Issue:
Description:Trough plasma concentration of MGD019
Time Frame:up to 108 weeks
Safety Issue:
Description:Total body clearance of the drug from plasma of MGD019
Time Frame:up to 108 weeks
Safety Issue:
Description:Apparent volume of distribution at steady state of MGD019
Time Frame:up to 108 weeks
Safety Issue:
Description:Terminal half life of MGD019
Measure:Percent of patients with anti-drug antibodies against MGD019
Time Frame:up to 108 weeks
Safety Issue:
Measure:Preliminary anti-tumor activity of MGD019
Time Frame:Every 12 - 24 weeks while patient is on treatment
Safety Issue:
Description:Efficacy assessed using conventional Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)


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

Trial Keywords

  • Checkpoint blockade

Last Updated

September 10, 2020