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MGD009/MGA012 Combination in Relapsed/Refractory 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. Identifier: NCT03406949
Recruitment Status : Recruiting
First Posted : January 23, 2018
Last Update Posted : August 13, 2019
Information provided by (Responsible Party):

Tracking Information
First Submitted Date  ICMJE January 16, 2018
First Posted Date  ICMJE January 23, 2018
Last Update Posted Date August 13, 2019
Actual Study Start Date  ICMJE February 27, 2018
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2018)
  • Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 [ Time Frame: 30 months ]
    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.
  • MTD/MAD [ Time Frame: 18 months ]
    Maximum Tolerated or Administrated Dose of MGD009 and MGA012
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03406949 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2018)
  • AUC [ Time Frame: 30 months ]
    Area Under the Plasma Concentration versus Time Curve of MGD009 and MGA012
  • Cmax [ Time Frame: 30 months ]
    Maximum Plasma Concentration of MGD009 and MGA012
  • Tmax [ Time Frame: 30 months ]
    Time to reach maximum (peak) plasma concentration of MGD009 and MGA012
  • Ctrough [ Time Frame: 30 months ]
    Trough plasma concentration of MGD009 and MGA012
  • CL [ Time Frame: 30 months ]
    Total body clearance of the drug from plasma of MGD009 and MGA012
  • Vss [ Time Frame: 30 months ]
    Apparent volume of distribution at steady state of MGD009 and MGA012
  • t1/2 [ Time Frame: 30 months ]
    Terminal half life of MGD009 and MGA012
  • ADA [ Time Frame: 30 months ]
    Percent of patients with anti-drug antibody to MGD009 and MGA012
  • Anti-tumor activity [ Time Frame: 30 months ]
    Conventional Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-related response criteria (irRECIST)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE MGD009/MGA012 Combination in Relapsed/Refractory Cancer
Official Title  ICMJE A Phase 1, Open Label, Dose Escalation Study of MGD009, a Humanized B7-H3 x CD3 DART® Protein, in Combination With MGA012, an Anti-PD-1 Antibody, in Patients With Relapsed or Refractory B7-H3-Expressing Tumors
Brief Summary The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of MGD009 administered in combination with MGA012 in patients with B7-H3- expressing tumors.
Detailed Description This study is a Phase 1, open-label, dose escalation, and cohort expansion study designed to characterize the safety, tolerability, PK, pharmacodynamics, immunogenicity, and preliminary antitumor activity of the combination of MGD009 and MGA012, each of which is administered by IV infusion.The study consists of a Dose Escalation Phase to determine the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) (if no MTD is defined) of the combination, followed by a Cohort Expansion Phase to further define the safety and initial antitumor activity of the combination with the doses established in the Dose Escalation Phase. Patients with B7-H3-expressing unresectable, locally advanced, or metastatic solid tumors of any histology will be enrolled in the Dose Escalation Phase. Following the establishment of an MTD, additional patients with specific tumor types will enroll in the Cohort Expansion Phase.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
3+3+3 dose escalation design followed by Cohort Expansion Phase.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE
  • Biological: MGD009
    B7-H3 x CD3 DART protein
    Other Name: orlotamab
  • Biological: MGA012
    anti-PD-1 antibody
    Other Name: INCMGA00012
Study Arms  ICMJE Experimental: MGD009 + MGA012
B7-H3 x CD3 DART protein + anti-PD-1 antibody
  • Biological: MGD009
  • Biological: MGA012
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 5, 2019)
Original Estimated Enrollment  ICMJE
 (submitted: January 16, 2018)
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically-proven, unresectable locally advanced or metastatic solid tumors of any histology that test positive for B7-H3 expression on tumor cells or vasculature for whom no approved therapy with demonstrated clinical benefit is available. For all tumor types, the requirement for previous systemic therapy may be waived if a patient was intolerant of or refused standard first-line therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy ≥ 12 weeks
  • Measurable disease, with the exception of prostate cancer
  • Tissue specimen available for B7-H3 and PD-L1 expression testing
  • Acceptable laboratory parameters
  • Patients who have previously received an immune checkpoint inhibitor (e.g., anti- PD-L1, anti-PD-1, anti-CTLA-4) prior to enrollment must have toxicities related to the checkpoint inhibitor resolved to ≤ Grade 1 or baseline (prior to the checkpoint inhibitor) to be eligible for enrollment. Patients who experienced previous hypothyroidism toxicity on a checkpoint inhibitor are eligible to enter study regardless of Grade resolution as long as the patient is well controlled on thyroid replacement hormones.

Exclusion Criteria:

  • Patients with history of prior central nervous system (CNS) metastasis must have been treated, must be asymptomatic, and must not have any of the following at the time of enrollment:

    1. No concurrent treatment for the CNS disease (e.g. surgery, radiation, corticosteroids >10 mg prednisone/day or equivalent)
    2. No progression of CNS metastases on MRI or CT for at least 14 days after last day of prior therapy for the CNS metastases
    3. No concurrent leptomeningeal disease or cord compression
  • Patients with any 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, investigational therapy within the 4 weeks prior to the initiation of study drug administration
  • Treatment with any systemic chemotherapy within 3 weeks
  • Treatment with radiation therapy within 2 weeks
  • History of allogeneic bone marrow, stem-cell, or solid organ transplant
  • Treatment with systemic corticosteroids (> 10 mg per day prednisone or equivalent) or other immune suppressive drugs within 2 weeks
  • Clinically significant cardiovascular or pulmonary disease
  • Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days prior to the initiation of study drug. Patients requiring any systemic antiviral, antifungal, or antibacterial therapy for active infection must have completed treatment no less than one week 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 or hepatitis C infection or known positive test for hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C polymerase chain reaction
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Amy Worth (240) 660-0757
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03406949
Other Study ID Numbers  ICMJE CP-MGD009-02
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party MacroGenics
Study Sponsor  ICMJE MacroGenics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Stacie Goldberg, MD MacroGenics
PRS Account MacroGenics
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP