Clinical Trials /

MGC018 With or Without MGA012 in Advanced Solid Tumors

NCT03729596

Description:

The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of MGC018 administered alone and in combination with MGA012 in patients with advanced solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: MGC018 With or Without MGA012 in Advanced Solid Tumors
  • Official Title: A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation Study of MGC018 (Anti-B7-H3 Antibody Drug Conjugate) Alone and in Combination With MGA012 (Anti-PD-1 Antibody) in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: CP-MGC018-01
  • NCT ID: NCT03729596

Conditions

  • Solid Tumor, Adult

Interventions

DrugSynonymsArms
MGC018MGC018 Monotherapy
MGA012INCMGA00012MGC018 plus MGA012

Purpose

The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of MGC018 administered alone and in combination with MGA012 in patients with advanced solid tumors.

Detailed Description

      This Phase 1/2, bifurcated-design study will characterize safety, dose-limiting toxicities
      (DLTs), and maximum tolerated/administered dose (MTD/MAD) for MGC018 as monotherapy (Module
      A) or in combination with MGA012 (Module B) in patients with advanced solid tumors. Module B
      will commence after the MTD/MAD of MGC018 monotherapy is defined. Each module consists of a
      Dose Escalation (3+3+3 design) followed by a Cohort Expansion Phase. Patients with solid
      tumors of any histology will be enrolled in the Dose Escalation Phases; Cohort Expansion will
      include disease-specific cohorts. Patients who do not experience DLT/unacceptable toxicity or
      meet criteria for permanent discontinuation may undergo additional cycles. Patients will be
      followed for survival every 3 months for 2 years following last dose.
    

Trial Arms

NameTypeDescriptionInterventions
MGC018 MonotherapyExperimentalMGC018: Anti-B7-H3 antibody drug conjugate
  • MGC018
MGC018 plus MGA012ExperimentalMGC018: Anti-B7-H3 antibody drug conjugate; MGA012: Anti-PD-1 antibody
  • MGC018
  • MGA012

Eligibility Criteria

        Inclusion Criteria:

          -  Tissue specimen available for retrospective analysis of B7-H3 and PD-L1 expression.

          -  Eastern Cooperative Oncology Group performance status of 0 or 1

          -  Life expectancy ≥ 12 weeks

          -  Measurable disease

          -  Dose Escalation Phase: Patients with histologically proven, unresectable, locally
             advanced or metastatic solid tumors 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
             therapy.

          -  Cohort Expansion Phase: Disease-specific prior therapy requirements to be specified.

          -  Acceptable laboratory parameters and adequate organ reserve.

          -  Patients with prior immune checkpoint inhibitors must have related toxicities reduced
             to Grade 0, 1, or baseline, with the exception of well-controlled hypothyroidism.

        Exclusion Criteria:

          -  Patients with history of prior central nervous system (CNS) metastasis must have been
             treated, be asymptomatic, and not have concurrent treatment for CNS disease,
             progression of CNS metastases on MRI or CT for at least 21 days after last day of
             prior therapy for the CNS metastases, or concurrent leptomeningeal disease or cord
             compression at the time of enrollment.

          -  History of autoimmune disease with certain exceptions such as vitiligo, resolved
             childhood atopic dermatitis, psoriasis not requiring systemic therapy within the past
             2 years, patients with history of Grave's disease that are now euthyroid clinically
             and by lab testing.

          -  Patients who experienced the following immune checkpoint inhibitor-related AEs make
             the patient ineligible despite the AE resolving to ≤ Grade 1 or baseline: ≥ Grade 3
             ocular AE, neurologic toxicity, colitis, pneumonitis, renal toxicity; changes in liver
             function tests that met criteria for Hy's Law.

          -  Prior treatment with orlotamab, enoblituzumab, or other B7-H3 targeted agents for
             cancer.

          -  Treatment with systemic cancer therapy within 3 weeks, investigational therapy within
             4 weeks; radiation within 2 weeks; corticosteroids (greater than or equal to 10 mg
             prednisone or equivalent per day) or other immune suppressive drugs within 2 weeks of
             first study drug administration.

          -  Clinically significant cardiovascular disease.

          -  Clinically significant pulmonary compromise or requirement for supplemental oxygen.

          -  History of clinically-significant cardiovascular disease.

          -  Active viral, bacterial, or systemic fungal infection requiring parenteral treatment
             within 7 days of first study drug administration.

          -  Known history of hepatitis B or C infection or known positive test for hepatitis B
             surface antigen or core antigen, or hepatitis C polymerase chain reaction.

          -  Known positive testing for human immunodeficiency virus or history of acquired immune
             deficiency syndrome.

          -  History of allogeneic bone marrow, stem cell, or solid organ transplant.

          -  Trauma or major surgery within 4 weeks of first study drug administration.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Adverse Events of MGC018 and MGC018 + MGA012 as assessed by CTCAE v4.03
Time Frame:30 days after last dose
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:Area under the curve
Time Frame:24 months
Safety Issue:
Description:Area under the plasma concentration versus time curve of MGC018 and MGC018+MGA012
Measure:Cmax
Time Frame:24 months
Safety Issue:
Description:Maximum Plasma Concentration of MGC018 and MGC018+MGA012
Measure:Tmax
Time Frame:24 months
Safety Issue:
Description:Time to reach maximum (peak) plasma concentration of MGC018 and MGC018+MGA012
Measure:Ctrough
Time Frame:24 months
Safety Issue:
Description:Trough plasma concentration of MGC018 and MGC018+MGA012
Measure:CL
Time Frame:24 months
Safety Issue:
Description:Total body clearance of the drug from plasma of MGC018 and MGC018+MGA012
Measure:Vss
Time Frame:24 months
Safety Issue:
Description:Apparent volume of distribution at steady state of MGC018 and MGC018+MGA012
Measure:t1/2
Time Frame:24 months
Safety Issue:
Description:Terminal half life of MGC018 and MGC018+MGA012
Measure:Percent of patients with anti-drug antibodies against MGC018 and MGA012
Time Frame:24 months
Safety Issue:
Description:immunogenicity
Measure:Preliminary anti-tumor activity of MGC018 and MGC018+MGA012
Time Frame:24 months
Safety Issue:
Description:Efficacy assessed as best overall response rate 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)

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:MacroGenics

Trial Keywords

  • antibody-drug conjugate (ADC)
  • B7-H3
  • anti-PD-1

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