<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03761017</url>
  </required_header>
  <id_info>
    <org_study_id>CP-MGD019-01</org_study_id>
    <nct_id>NCT03761017</nct_id>
  </id_info>
  <brief_title>MGD019 DART® Protein in Unresectable/Metastatic Cancer</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>MacroGenics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>MacroGenics</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK)&#xD;
      pharmacodynamics and preliminary antitumor activity of lorigerlimab.&#xD;
&#xD;
      This Phase 1, open-label study will characterize safety, dose-limiting toxicities (DLTs), and&#xD;
      maximum tolerated/administered dose (MTD/MAD) of MGD019. Dose escalation will occur in a&#xD;
      3+3+3 design in patients with advanced solid tumors of any histology. Once the MTD/MAD is&#xD;
      determined, a Cohort Expansion Phase will be enrolled to further characterize safety and&#xD;
      initial anti-tumor activity in patients with specific tumor types anticipated to be sensitive&#xD;
      to dual checkpoint blockade.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 12, 2018</start_date>
  <completion_date type="Anticipated">April 2024</completion_date>
  <primary_completion_date type="Anticipated">October 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of treatment-emergent adverse events</measure>
    <time_frame>30 days after last dose</time_frame>
    <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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax</measure>
    <time_frame>up to 108 weeks</time_frame>
    <description>Maximum Plasma Concentration of lorigerlimab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax</measure>
    <time_frame>up to 108 weeks</time_frame>
    <description>Time to reach maximum (peak) plasma concentration of lorigerlimab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC</measure>
    <time_frame>up to 108 weeks</time_frame>
    <description>Area Under the Plasma Concentration versus Time Curve of lorigerlimab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ctrough</measure>
    <time_frame>up to 108 weeks</time_frame>
    <description>Trough plasma concentration of lorigerlimab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL</measure>
    <time_frame>up to 108 weeks</time_frame>
    <description>Total body clearance of the drug from plasma of lorigerlimab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vss</measure>
    <time_frame>up to 108 weeks</time_frame>
    <description>Apparent volume of distribution at steady state of lorigerlimab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2</measure>
    <time_frame>up to 108 weeks</time_frame>
    <description>Terminal half life of lorigerlimab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of patients with anti-drug antibodies against lorigerlimab</measure>
    <time_frame>up to 108 weeks</time_frame>
    <description>Immunogenicity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>Every 12 weeks, up to 4 years</time_frame>
    <description>The number of participants who have a complete response (CR) or partial response (PR) to treatment. Efficacy assessed using conventional Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DoR)</measure>
    <time_frame>Every 12 weeks until withdrawal of consent, lost to follow up, death, or end of the study, up to 4 years</time_frame>
    <description>DoR is defined as the time from the date of initial response (CR or PR) to the date of first documented PD or death from any cause, whichever occurs first</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>Tumor status assessed every 12 weeks. Survival status is assessed approximately every 12 weeks after the last dose of study treatment until withdrawal of consent, lost to follow up, death, or end of the study, up to 4 years</time_frame>
    <description>PFS is defined as the time from the first dose date to the date of first documented PD or death from any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>OS status is assessed approximately every 12 weeks after the last dose of study treatment until withdrawal of consent, lost to follow up, death, or end of the study, up to 4 years</time_frame>
    <description>OS is defined as the time from the first dose date to the date of death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prostate specific antigen (PSA) response rate in mCRPC</measure>
    <time_frame>Every 3 weeks on treatment, then every 3 months up to 2 years post last treatment</time_frame>
    <description>Percent of patients with 50% or more decline in PSA and confirmed 3 weeks later</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best PSA percent change in mCRPC</measure>
    <time_frame>Every 3 weeks on treatment, then every 3 months up to 2 years post last treatment</time_frame>
    <description>Best percent change in PSA from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of PSA response</measure>
    <time_frame>Every 3 weeks on treatment, then every 3 months up to 2 years post last treatment</time_frame>
    <description>Time from PSA response to time of PSA progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiographic progression-free survival (PFS) in metastatic castration-resistant prostate cancer (mCRPC)</measure>
    <time_frame>up to 2 years post last treatment</time_frame>
    <description>Time from first dose to first occurrence of radiographic progression, or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to PSA progression in mCRPC</measure>
    <time_frame>PSA is assessed every 3 weeks while on treatment, every 3 months for up to 2 years post-treatment</time_frame>
    <description>The time from the first dose of MGD019 to the first documented PSA progression. PSA progression is defined as an increase that is ≥ 25% and ≥ 2 ng/mL the baseline or lowest value observed, and which confirmed by a second value at least 3 weeks later</description>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Actual">162</enrollment>
  <condition>Squamous Cell Non Small Cell Lung Cancer</condition>
  <condition>Prostate Cancer Metastatic</condition>
  <condition>Cutaneous Melanoma</condition>
  <condition>Colorectal Cancer</condition>
  <condition>Advanced Cancer</condition>
  <condition>Solid Tumor, Adult</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.03 mg/kg administered IV every 3 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.1 mg/kg administered IV every 3 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.3 mg/kg administered IV every 3 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1.0 mg/kg administered IV every 3 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>30. mg/kg administered IV every 3 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 6</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6.0 mg/kg administered IV every 3 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 7</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10.0 mg/kg administered IV every 3 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Lorigerlimab</intervention_name>
    <description>Bispecific DART protein binding PD-1 and CTLA-4</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_label>Cohort 4</arm_group_label>
    <arm_group_label>Cohort 5</arm_group_label>
    <arm_group_label>Cohort 6</arm_group_label>
    <arm_group_label>Cohort 7</arm_group_label>
    <other_name>MGD019</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Dose escalation: Patients with histologically proven, unresectable, locally advanced&#xD;
             or metastatic solid tumors for whom no approved therapy with demonstrated clinical&#xD;
             benefit is available or patients who are intolerant to standard therapy.&#xD;
&#xD;
          -  Cohort Expansion Phase:&#xD;
&#xD;
          -  Checkpoint inhibitor-naïve squamous cell NSCLC, including:&#xD;
&#xD;
               1. Patients that have progressed during or following treatment with platinum-based&#xD;
                  chemotherapy for advanced disease. Patients harboring an activating epidermal&#xD;
                  growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK)&#xD;
                  rearrangement must have progressed following at least one available EGFR or ALK&#xD;
                  targeted therapy. ROS1 rearrangement or BRAF mutation must have progressed&#xD;
                  following at least 1 available EGFR (including osimertinib for EGFR T790M-mutated&#xD;
                  NSCLC), ALK, ROS1 or BRAF targeted therapy, respectively&#xD;
&#xD;
               2. Patients that have progressed during or following treatment with platinum-based&#xD;
                  chemotherapy for advanced disease and patients with previously untreated squamous&#xD;
                  cell NSCLC without activating mutations for whom checkpoint inhibitor therapy is&#xD;
                  not approved or available.&#xD;
&#xD;
          -  Advanced non-microsatellite instability-high colorectal cancer (CRC) with recurrence,&#xD;
             progression, or intolerance to standard therapy consisting of at least 2 prior&#xD;
             standard regimens. CRC harboring an activating EGFR mutation must have progressed&#xD;
             during or following at least one available EGFR targeted therapy. Patients who are&#xD;
             inappropriate candidates for or have refused treatment with these regimens are also&#xD;
             eligible. Patients should have received no more than 4 prior lines of systemic&#xD;
             therapy.&#xD;
&#xD;
          -  Checkpoint inhibitor-naïve mCRPC that has progressed during or following no more than&#xD;
             2 prior lines of an androgen receptor antagonist or androgen synthesis inhibitor&#xD;
             (e.g., enzalutamide or abiraterone, respectively), if approved and available, with a&#xD;
             PSA value of at least 2 ng/mL and meeting at least one of the following:&#xD;
&#xD;
          -  Progression in measurable disease (RECIST v1.1).&#xD;
&#xD;
          -  Appearance of 2 or more new bone lesions according to Prostate Cancer Working Group 2&#xD;
             (PCWG-2).&#xD;
&#xD;
          -  Rising PSA defined as at least two sequential rises in PSA.&#xD;
&#xD;
          -  Eligible patients may have received prior chemotherapy (i.e. docetaxel), and patients&#xD;
             with known homologous recombination (HRR) pathway gene alterations must have received&#xD;
             the applicable approved therapy (e.g. olaparib).&#xD;
&#xD;
          -  Cutaneous melanoma that has progressed during or following systemic treatment for&#xD;
             unresectable, locally advanced, or metastatic disease. Patients will have received&#xD;
             PD-(L)1 and/or CTLA-4 pathway inhibitors where available and indicated.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1&#xD;
&#xD;
          -  Life expectancy ≥ 12 weeks.&#xD;
&#xD;
          -  Measurable disease as per RECIST 1.1 for the purpose of response assessment must&#xD;
             either (a) not reside in a field that has been subjected to prior radiotherapy or (b)&#xD;
             have demonstrated clear evidence of radiographic progression since the completion of&#xD;
             prior radiotherapy and prior to study enrollment.&#xD;
&#xD;
          -  All patients must have an identified formalin-fixed, paraffin embedded (FFPE) tumor&#xD;
             specimen (up to 20 slides or a block) for immunohistochemical evaluation of&#xD;
             pharmacodynamic markers of interest. Patients may undergo a fresh tumor biopsy during&#xD;
             the screening period if a tumor sample is not available. Patients in the mCRPC&#xD;
             expansion cohort with bone only disease not amenable to fresh biopsy may be eligible&#xD;
             in consultation with the Sponsor.&#xD;
&#xD;
          -  Acceptable laboratory parameters and adequate organ reserve.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  In patients who have previously received an immune checkpoint inhibitor (e.g.,&#xD;
             anti-PD-L1, anti-PD-1, anti-CTLA-4), toxicities related to the checkpoint inhibitor&#xD;
             must have resolved to ≤ Grade 1 or baseline. Patients with well controlled immune&#xD;
             endocrinopathies secondary to prior checkpoint therapy are eligible.&#xD;
&#xD;
          -  Patients with symptomatic CNS metastases. Patients with history of prior CNS&#xD;
             metastasis must have been treated, must be asymptomatic, and must not have concurrent&#xD;
             treatment for the CNS disease, progression of CNS metastases on magnetic resonance&#xD;
             imaging (MRI) or computed tomography (CT) for at least 14 days after last day of prior&#xD;
             therapy for the CNS metastases, or concurrent leptomeningeal disease or cord&#xD;
             compression.&#xD;
&#xD;
          -  Patients who sustained the following Grade 3 immune checkpoint inhibitor related AEs&#xD;
             are ineligible: Ocular AE, changes in liver function tests that met the criteria for&#xD;
             Hy's law (&gt; 3 × ULN of either ALT or AST with concurrent &gt; 2 × ULN of total bilirubin&#xD;
             and without alternate etiology), neurologic toxicity, colitis, renal toxicity,&#xD;
             pneumonitis.&#xD;
&#xD;
          -  Patients who have received prior therapy with a combination of monoclonal antibodies&#xD;
             against PD-1/PD-L1 and CTLA-4 will be excluded in the Cohort Expansion (this does not&#xD;
             apply to the melanoma expansion cohort).&#xD;
&#xD;
          -  Patients with any history of known or suspected autoimmune disease with certain&#xD;
             exceptions&#xD;
&#xD;
          -  History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation.&#xD;
&#xD;
          -  History of trauma or major surgical procedure within 4 weeks prior to initiation of&#xD;
             study drug administration.&#xD;
&#xD;
          -  Systemic antineoplastic therapy, or investigational therapy (for all tumor types) or&#xD;
             androgen receptor antagonist/androgen synthesis inhibitor for mCRPC (e.g.,&#xD;
             enzalutamide or abiraterone, respectively) within the 4 weeks prior to initiation of&#xD;
             study drug administration.&#xD;
&#xD;
          -  Treatment with radiation therapy within 2 weeks prior to initiation of study drug&#xD;
             administration.&#xD;
&#xD;
          -  Radioligand (e.g., radium-223) within 6 months prior to initiation of study drug&#xD;
             administration for mCRPC in the Cohort Expansion Phase.&#xD;
&#xD;
          -  Serum testosterone &gt; 50 ng/dl or &gt; 1.7 nmol/L for mCRPC in the Cohort Expansion Phase.&#xD;
&#xD;
          -  Confirmed or presumed COVID-19/SARS-CoV-2 infection. While SARS-CoV-2 testing is not&#xD;
             mandatory for study entry, testing should follow local clinical practice&#xD;
             guidelines/standards. Patients with a positive test result for SARS-CoV-2 infection,&#xD;
             known asymptomatic infection, or presumed infection are excluded. Patients may be&#xD;
             considered eligible after a resolved SARS-CoV-2 infection once he or she remains&#xD;
             afebrile for at least 72 hours and after other SARS-CoV-2-related symptoms have fully&#xD;
             recovered to baseline for a minimum of 72 hours&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Denise Casey, MD</last_name>
    <role>Study Director</role>
    <affiliation>MacroGenics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Chicago Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>START Midwest</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49546</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Hematology West p.c. dba Nebraska Cancer Specialists</name>
      <address>
        <city>Grand Island</city>
        <state>Nebraska</state>
        <zip>68803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nebraska Cancer Specialists</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Portland Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center</name>
      <address>
        <city>Camp Hill</city>
        <state>Pennsylvania</state>
        <zip>17011</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center</name>
      <address>
        <city>Carlisle</city>
        <state>Pennsylvania</state>
        <zip>17015</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center</name>
      <address>
        <city>Erie</city>
        <state>Pennsylvania</state>
        <zip>16505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Pinnacle Harrisburg</name>
      <address>
        <city>Harrisburg</city>
        <state>Pennsylvania</state>
        <zip>17101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Pinnacle - Community Osteopathic Medical Sciences Pavilion (MSP)</name>
      <address>
        <city>Harrisburg</city>
        <state>Pennsylvania</state>
        <zip>17109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Pinnacle - Ortenzio Cancer Center (OCC)</name>
      <address>
        <city>Mechanicsburg</city>
        <state>Pennsylvania</state>
        <zip>17050</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>20850</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center at UPMC Memorial</name>
      <address>
        <city>York</city>
        <state>Pennsylvania</state>
        <zip>17408</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Sarah Cannon Research Institute / Tennessee Oncology</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complex Oncology Center - Burgas&quot; EOOD, Department of Medical Oncology</name>
      <address>
        <city>Burgas</city>
        <zip>8000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Multiprofile Hospital for Active Treatment-Uni Hospital</name>
      <address>
        <city>Panagyurishte</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Multiprofile Hospital for Active Treatment &quot;Heart and Brain&quot;&quot; EAD, Clinic of Medical Oncology</name>
      <address>
        <city>Pleven</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complex Oncology Center - Ruse EOOD</name>
      <address>
        <city>Ruse</city>
        <zip>7002</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Clinical Centre, Early Clinical Trials Unit</name>
      <address>
        <city>Gdańsk</city>
        <zip>80-214</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pratia MCM Krakow</name>
      <address>
        <city>Kraków</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Europejskie Centrum Zdrowia Otwock</name>
      <address>
        <city>Otwock</city>
        <zip>05-400</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Med-Polonia Sp. z.o.o.</name>
      <address>
        <city>Poznań</city>
        <zip>60-693</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LUX MED Onkologia Sp. z.o.o.</name>
      <address>
        <city>Warszawa</city>
        <zip>01-748</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Narodowy Instytut Onkologii im</name>
      <address>
        <city>Warszawa</city>
        <zip>02-781</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mazovian Onkological Hospital</name>
      <address>
        <city>Wieliszew</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICO Badalona / Hospital Universitari Germans Trias i Pujol</name>
      <address>
        <city>Badalona</city>
        <state>Barcelona</state>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Ruber Internacional</name>
      <address>
        <city>Madrid</city>
        <zip>20834</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Princesa</name>
      <address>
        <city>Madrid</city>
        <zip>28006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Communal Non-profit Enterprise &quot;City Clinical Hospital #4&quot; of Dnipro</name>
      <address>
        <city>Dnipro</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Communal Non-Profit Enterprise &quot;Regional Center of Oncology&quot;, Oncosurgical Department of Head and Neck</name>
      <address>
        <city>Kharkiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Communal Nonprofit Enterprise &quot;Regional Clinical Oncology Center of Kirovohrad Regional Council&quot;</name>
      <address>
        <city>Kirovohrad</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kyiv City Clinical Oncological Centre</name>
      <address>
        <city>Kyiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Institute of Ukraine</name>
      <address>
        <city>Kyiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sumy Clinical Oncological Hospital</name>
      <address>
        <city>Sumy</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Communal Nonprofit Enterprise &quot;Podilsky Regional Center of Oncology&quot;</name>
      <address>
        <city>Vinnytsia</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>Ukraine</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762776/</url>
    <description>Link to published 2020 manuscript</description>
  </link>
  <reference>
    <citation>Berezhnoy A, Sumrow BJ, Stahl K, Shah K, Liu D, Li J, Hao SS, De Costa A, Kaul S, Bendell J, Cote GM, Luke JJ, Sanborn RE, Sharma MR, Chen F, Li H, Diedrich G, Bonvini E, Moore PA. Development and Preliminary Clinical Activity of PD-1-Guided CTLA-4 Blocking Bispecific DART Molecule. Cell Rep Med. 2020 Dec 22;1(9):100163. doi: 10.1016/j.xcrm.2020.100163. eCollection 2020 Dec 22.</citation>
    <PMID>33377134</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>November 29, 2018</study_first_submitted>
  <study_first_submitted_qc>November 30, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 3, 2018</study_first_posted>
  <last_update_submitted>March 3, 2023</last_update_submitted>
  <last_update_submitted_qc>March 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03761017
org study id: CP-MGD019-01
nct id: NCT03761017
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK)
      pharmacodynamics and preliminary antitumor activity of lorigerlimab.

      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.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of treatment-emergent adverse events
time frame: 30 days after last dose
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.
measure: Cmax
time frame: up to 108 weeks
description: Maximum Plasma Concentration of lorigerlimab
measure: Tmax
time frame: up to 108 weeks
description: Time to reach maximum (peak) plasma concentration of lorigerlimab
measure: AUC
time frame: up to 108 weeks
description: Area Under the Plasma Concentration versus Time Curve of lorigerlimab
measure: Ctrough
time frame: up to 108 weeks
description: Trough plasma concentration of lorigerlimab
measure: CL
time frame: up to 108 weeks
description: Total body clearance of the drug from plasma of lorigerlimab
measure: Vss
time frame: up to 108 weeks
description: Apparent volume of distribution at steady state of lorigerlimab
measure: t1/2
time frame: up to 108 weeks
description: Terminal half life of lorigerlimab
measure: Percent of patients with anti-drug antibodies against lorigerlimab
time frame: up to 108 weeks
description: Immunogenicity
measure: Objective response rate (ORR)
time frame: Every 12 weeks, up to 4 years
description: The number of participants who have a complete response (CR) or partial response (PR) to treatment. Efficacy assessed using conventional Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
measure: Duration of Response (DoR)
time frame: Every 12 weeks until withdrawal of consent, lost to follow up, death, or end of the study, up to 4 years
description: DoR is defined as the time from the date of initial response (CR or PR) to the date of first documented PD or death from any cause, whichever occurs first
measure: Progression free survival (PFS)
time frame: Tumor status assessed every 12 weeks. Survival status is assessed approximately every 12 weeks after the last dose of study treatment until withdrawal of consent, lost to follow up, death, or end of the study, up to 4 years
description: PFS is defined as the time from the first dose date to the date of first documented PD or death from any cause, whichever occurs first.
measure: Overall survival (OS)
time frame: OS status is assessed approximately every 12 weeks after the last dose of study treatment until withdrawal of consent, lost to follow up, death, or end of the study, up to 4 years
description: OS is defined as the time from the first dose date to the date of death from any cause.
measure: Prostate specific antigen (PSA) response rate in mCRPC
time frame: Every 3 weeks on treatment, then every 3 months up to 2 years post last treatment
description: Percent of patients with 50% or more decline in PSA and confirmed 3 weeks later
measure: Best PSA percent change in mCRPC
time frame: Every 3 weeks on treatment, then every 3 months up to 2 years post last treatment
description: Best percent change in PSA from baseline
measure: Duration of PSA response
time frame: Every 3 weeks on treatment, then every 3 months up to 2 years post last treatment
description: Time from PSA response to time of PSA progression
measure: Radiographic progression-free survival (PFS) in metastatic castration-resistant prostate cancer (mCRPC)
time frame: up to 2 years post last treatment
description: Time from first dose to first occurrence of radiographic progression, or death
measure: Time to PSA progression in mCRPC
time frame: PSA is assessed every 3 weeks while on treatment, every 3 months for up to 2 years post-treatment
description: The time from the first dose of MGD019 to the first documented PSA progression. PSA progression is defined as an increase that is ≥ 25% and ≥ 2 ng/mL the baseline or lowest value observed, and which confirmed by a second value at least 3 weeks later
arm group label: Cohort 1
arm group type: Experimental
description: 0.03 mg/kg administered IV every 3 weeks.
arm group label: Cohort 2
arm group type: Experimental
description: 0.1 mg/kg administered IV every 3 weeks.
arm group label: Cohort 3
arm group type: Experimental
description: 0.3 mg/kg administered IV every 3 weeks.
arm group label: Cohort 4
arm group type: Experimental
description: 1.0 mg/kg administered IV every 3 weeks.
arm group label: Cohort 5
arm group type: Experimental
description: 30. mg/kg administered IV every 3 weeks.
arm group label: Cohort 6
arm group type: Experimental
description: 6.0 mg/kg administered IV every 3 weeks.
arm group label: Cohort 7
arm group type: Experimental
description: 10.0 mg/kg administered IV every 3 weeks.
intervention type: Biological
intervention name: Lorigerlimab
description: Bispecific DART protein binding PD-1 and CTLA-4
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
arm group label: Cohort 4
arm group label: Cohort 5
arm group label: Cohort 6
arm group label: Cohort 7
other name: MGD019
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Denise Casey, MD
role: Study Director
affiliation: MacroGenics
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country: Bulgaria
country: Poland
country: Spain
country: Ukraine
country: United States
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762776/
description: Link to published 2020 manuscript
citation: Berezhnoy A, Sumrow BJ, Stahl K, Shah K, Liu D, Li J, Hao SS, De Costa A, Kaul S, Bendell J, Cote GM, Luke JJ, Sanborn RE, Sharma MR, Chen F, Li H, Diedrich G, Bonvini E, Moore PA. Development and Preliminary Clinical Activity of PD-1-Guided CTLA-4 Blocking Bispecific DART Molecule. Cell Rep Med. 2020 Dec 22;1(9):100163. doi: 10.1016/j.xcrm.2020.100163. eCollection 2020 Dec 22.
PMID: 33377134
responsible party type: Sponsor
mesh term: Melanoma
sharing ipd: No