Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

MGD019 DART® Protein in Unresectable/Metastatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03761017
Recruitment Status : Recruiting
First Posted : December 3, 2018
Last Update Posted : June 4, 2019
Sponsor:
Information provided by (Responsible Party):
MacroGenics

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

Condition or disease Intervention/treatment Phase
Solid Tumor, Adult Advanced Cancer Biological: MGD019 Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 167 participants
Intervention Model: Single Group Assignment
Intervention Model Description: 3+3+3 dose escalation design followed by cohort expansion at MTD/MAD
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 12, 2018
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : December 2023

Arm Intervention/treatment
Experimental: MGD019
Bispecific DART protein binding PD-1 and CTLA-4
Biological: MGD019
Bispecific DART protein binding PD-1 and CTLA-4




Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events [ Time Frame: 30 days after last dose ]
    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 :
  1. Cmax [ Time Frame: up to 108 weeks ]
    Maximum Plasma Concentration of MGD019

  2. Tmax [ Time Frame: up to 108 weeks ]
    Time to reach maximum (peak) plasma concentration of MGD019

  3. AUC [ Time Frame: up to 108 weeks ]
    Area Under the Plasma Concentration versus Time Curve of MGD019

  4. Ctrough [ Time Frame: up to 108 weeks ]
    Trough plasma concentration of MGD019

  5. CL [ Time Frame: up to 108 weeks ]
    Total body clearance of the drug from plasma of MGD019

  6. Vss [ Time Frame: up to 108 weeks ]
    Apparent volume of distribution at steady state of MGD019

  7. t1/2 [ Time Frame: up to 108 weeks ]
    Terminal half life of MGD019

  8. Percent of patients with anti-drug antibodies against MGD019 [ Time Frame: up to 108 weeks ]
    Immunogenicity

  9. Preliminary anti-tumor activity of MGD019 [ Time Frame: Every 12 - 24 weeks while patient is on treatment ]
    Efficacy assessed using both conventional Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) (Appendix 5) and immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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: Disease-specific prior therapy requirements to be specified.
  • 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 compression.
  • 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, pneumonitis.
  • 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 exceptions
  • 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 administration.
  • Treatment with radiation therapy within 2 weeks prior to initiation of study drug administration.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03761017


Contacts
Layout table for location contacts
Contact: Kerri Cali 240.552.8666 calik@macrogenics.com

Locations
Layout table for location information
United States, Michigan
START Midwest Recruiting
Grand Rapids, Michigan, United States, 49546
Contact: Katie L. Robinson, BSN, RN    616-389-1739    Katie.Robinson@startmidwest.com   
Principal Investigator: Manish Sharma, MD         
United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: Christina Lopez    503-215-2614    CanRsrchStudies@providence.org   
Principal Investigator: Rachel Sanborn, MD         
United States, Tennessee
The Sarah Cannon Research Institute / Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: Sheetal Champaneria    615-329-6875    Sheetal.Champaneria@sarahcannon.com   
Principal Investigator: Johanna Bendell, MD         
Sponsors and Collaborators
MacroGenics
Investigators
Layout table for investigator information
Study Director: Bradley Sumrow, MD MacroGenics

Layout table for additonal information
Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT03761017     History of Changes
Other Study ID Numbers: CP-MGD019-01
First Posted: December 3, 2018    Key Record Dates
Last Update Posted: June 4, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by MacroGenics:
Checkpoint blockade