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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. Read our disclaimer for details. Identifier: NCT03406949
Recruitment Status : Active, not recruiting
First Posted : January 23, 2018
Last Update Posted : April 19, 2021
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Biological: MGD009 Biological: MGA012 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: N/A
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
Official Title: 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
Actual Study Start Date : February 27, 2018
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Arm Intervention/treatment
Experimental: MGD009 + MGA012
B7-H3 x CD3 DART protein + anti-PD-1 antibody
Biological: MGD009
B7-H3 x CD3 DART protein
Other Name: orlotamab

Biological: MGA012
anti-PD-1 antibody
Other Name: INCMGA00012

Primary Outcome Measures :
  1. 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.

  2. MTD/MAD [ Time Frame: 18 months ]
    Maximum Tolerated or Administrated Dose of MGD009 and MGA012

Secondary Outcome Measures :
  1. AUC [ Time Frame: 30 months ]
    Area Under the Plasma Concentration versus Time Curve of MGD009 and MGA012

  2. Cmax [ Time Frame: 30 months ]
    Maximum Plasma Concentration of MGD009 and MGA012

  3. Tmax [ Time Frame: 30 months ]
    Time to reach maximum (peak) plasma concentration of MGD009 and MGA012

  4. Ctrough [ Time Frame: 30 months ]
    Trough plasma concentration of MGD009 and MGA012

  5. CL [ Time Frame: 30 months ]
    Total body clearance of the drug from plasma of MGD009 and MGA012

  6. Vss [ Time Frame: 30 months ]
    Apparent volume of distribution at steady state of MGD009 and MGA012

  7. t1/2 [ Time Frame: 30 months ]
    Terminal half life of MGD009 and MGA012

  8. ADA [ Time Frame: 30 months ]
    Percent of patients with anti-drug antibody to MGD009 and MGA012

  9. Anti-tumor activity [ Time Frame: 30 months ]
    Conventional Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-related response criteria (irRECIST)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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 identifier (NCT number): NCT03406949

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United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
University of Southern California
Los Angeles, California, United States, 90033
Hoag Memorial Hospital Presbyterian
Newport Beach, California, United States, 92663
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02214
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
START (South Texas Accelerated Research Therapeutics) - Midwest
Grand Rapids, Michigan, United States, 49546
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
Mary Crowley Cancer Center
Dallas, Texas, United States, 75251
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Virginia
Virginia Cancer Specialists
Fairfax, Virginia, United States, 22031
Sponsors and Collaborators
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Study Director: Stacie Goldberg, MD MacroGenics
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Responsible Party: MacroGenics Identifier: NCT03406949    
Other Study ID Numbers: CP-MGD009-02
First Posted: January 23, 2018    Key Record Dates
Last Update Posted: April 19, 2021
Last Verified: April 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No