Clinical Trials /

MGD009/MGA012 Combination in Relapsed/Refractory Cancer

NCT03406949

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: MGD009/MGA012 Combination in Relapsed/Refractory Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: CP-MGD009-02
  • NCT ID: NCT03406949

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
MGD009orlotamabMGD009 + MGA012
MGA012INCMGA00012MGD009 + MGA012

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
MGD009 + MGA012ExperimentalB7-H3 x CD3 DART protein + anti-PD-1 antibody
  • MGD009
  • MGA012

Eligibility Criteria

        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
      
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 as assessed by CTCAE v4.03
Time Frame:30 months
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

Measure:AUC
Time Frame:30 months
Safety Issue:
Description:Area Under the Plasma Concentration versus Time Curve of MGD009 and MGA012
Measure:Cmax
Time Frame:30 months
Safety Issue:
Description:Maximum Plasma Concentration of MGD009 and MGA012
Measure:Tmax
Time Frame:30 months
Safety Issue:
Description:Time to reach maximum (peak) plasma concentration of MGD009 and MGA012
Measure:Ctrough
Time Frame:30 months
Safety Issue:
Description:Trough plasma concentration of MGD009 and MGA012
Measure:CL
Time Frame:30 months
Safety Issue:
Description:Total body clearance of the drug from plasma of MGD009 and MGA012
Measure:Vss
Time Frame:30 months
Safety Issue:
Description:Apparent volume of distribution at steady state of MGD009 and MGA012
Measure:t1/2
Time Frame:30 months
Safety Issue:
Description:Terminal half life of MGD009 and MGA012
Measure:ADA
Time Frame:30 months
Safety Issue:
Description:Percent of patients with anti-drug antibody to MGD009 and MGA012
Measure:Anti-tumor activity
Time Frame:30 months
Safety Issue:
Description:Conventional Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-related response criteria (irRECIST)

Details

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

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