Clinical Trials /

Safety Study of MGD009 in B7-H3-expressing Tumors

NCT02628535

Description:

The purpose of this study is to evaluate the safety of MGD009 when given to patients with B7-H3-expressing tumors. The study will also evaluate what is the highest dose of MGD009 that can be given safely. Assessments will be done to see how the drug acts in the body (pharmacokinetics (PK), pharmacodynamics (PD) and to evaluate potential anti-tumor activity of MGD009.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety Study of MGD009 in B7-H3-expressing Tumors
  • Official Title: Phase 1, First-in-Human, Open Label, Dose Escalation Study of MGD009, A Humanized B7-H3 x CD3 Dual-Affinity Re-Targeting (DART) Protein in Patients With Unresectable or Metastatic B7-H3-Expressing Neoplasms

Clinical Trial IDs

  • ORG STUDY ID: CP-MGD009-01
  • NCT ID: NCT02628535

Conditions

  • Mesothelioma
  • Bladder Cancer
  • Melanoma
  • Squamous Cell Carcinoma of the Head and Neck
  • Non Small Cell Lung Cancer
  • Clear Cell Renal Cell Carcinoma
  • Ovarian Cancer
  • Thyroid Cancer
  • Breast Cancer
  • Pancreatic Cancer
  • Prostate Cancer
  • Colon Cancer
  • Soft Tissue Sarcoma

Interventions

DrugSynonymsArms
MGD009orlotamabMGD009

Purpose

The purpose of this study is to evaluate the safety of MGD009 when given to patients with B7-H3-expressing tumors. The study will also evaluate what is the highest dose of MGD009 that can be given safely. Assessments will be done to see how the drug acts in the body (pharmacokinetics (PK), pharmacodynamics (PD) and to evaluate potential anti-tumor activity of MGD009.

Detailed Description

      This study is a Phase 1 open-label, dose escalation, cohort expansion, and efficacy follow-up
      study of MGD009 administered intravenously (IV) on an every-other-week schedule for up to one
      year (14 cycles).

      The dose escalation phase is designed to characterize the safety and tolerability of MGD009
      and to define the maximum tolerated or maximum administered dose (MTD/MAD). This phase will
      enroll patients with mesothelioma, bladder cancer, melanoma, squamous cell carcinoma of the
      head and neck (SCCHN), non-small cell lung cancer (NSCLC), clear cell renal cell carcinoma
      (ccRCC), ovarian cancer, thyroid cancer, triple-negative breast cancer (TNBC), pancreatic
      cancer, colon cancer, soft tissue sarcoma, or prostate cancer.

      In the cohort expansion phase, 6 cohorts of 16 patients each will be enrolled to further
      evaluate the safety and potential efficacy of MGD009 administered at the MTD/MAD dose in
      patients with mesothelioma, bladder cancer, melanoma, SCCHN, NSCLC, or other specific tumors
      that express high levels of B7-H3. Pre- and on-study biopsies are required for melanoma
      patients in the cohort expansion phase. Two additional cohorts (up to15 patients each) will
      evaluate the use of prophylaxis therapies to mitigate toxicity.

      The survival follow-up phase consists of the 2-year period after the final dose of study
      drug.

      All tumor evaluations will be carried out by both Response Evaluation Criteria in Solid
      Tumors (RECIST) and immune-related response criteria (irRC).
    

Trial Arms

NameTypeDescriptionInterventions
MGD009ExperimentalOrlotamab; Humanized B7-H3 x CD3 Dual-Affinity Re-Targeting (DART®) Protein
  • MGD009

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically and/or cytologically proven unresectable locally advanced or metastatic
             tumors that express B7-H3 on the membrane or vasculature. The requirement for previous
             systemic therapy may be waived if a person was intolerant of standard front-line
             therapy

          -  Dose escalation phase prior systemic treatment requirements:

          -  pleural mesothelioma, pancreatic cancer: 1-3 prior treatments

          -  urothelial, SCHNN, prostate, soft tissue sarcoma, prostate cancer, TNBC, ccRCC, NSCLC:
             1-5 prior treatments

          -  ovarian cancer: 2-4 prior treatments

          -  colon cancer: 2-4 prior treatments

          -  cutaneous melanoma: at least 1 prior treatment (including immunotherapy).

          -  Patients with prior immune checkpoint inhibitors must have related toxicities reduced
             to Grade 0, 1, or baseline

          -  Measurable disease per RECIST 1.1 criteria

          -  Easter Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Acceptable laboratory parameters and adequate organ reserve.

        Exclusion Criteria:

          -  Patients with central nervous system (CNS) involvement must have been treated, be
             asymptomatic, do not exhibit progression of CNS metastases on MRI or CT within 28
             days, and do not have concurrent leptomeningeal disease or cord compression.

          -  Clinically significant pulmonary compromise within 28 days of first dose, including
             pneumonia, pneumonitis, requirement for supplemental oxygen). use to maintain adequate
             oxygenation, or pleural effusion sufficient to warrant pleurocentesis or any history
             of ≥ Grade 3 drug induced or radiation pneumonitis.

          -  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 Hashimoto's or Grave's disease that are now
             euthyroid clinically and by lab testing

          -  History of clinically-significant cardiovascular disease, or cardiac arrhythmias,
             including atrial fibrillation at screening or day of treatment

          -  History of clinically-significant gastrointestinal (GI) disease; GI perforation within
             1 year; GI bleeding or acute pancreatitis within 3 months; or diverticulitis within 4
             weeks of first study drug administration

          -  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 (PCR)

          -  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

          -  Treatment with systemic cancer therapy or investigational therapy within 3 weeks of
             first study drug administration; 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

          -  Trauma or major surgery within 4 weeks of first study drug administration

          -  Known hypersensitivity to recombinant proteins, polysorbate 80, or any excipient
             contained in the drug or vehicle formulation for MGD009
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with adverse events
Time Frame:28 days after last dose of study drug
Safety Issue:
Description:adverse events, serious adverse events

Secondary Outcome Measures

Measure:Peak plasma concentration
Time Frame:8 days
Safety Issue:
Description:PK of MGD009
Measure:Number of participants that develop anti-drug antibodies
Time Frame:first dose through 28 days after last dose of study drug
Safety Issue:
Description:Proportion of patients who develop anti-MGD0009 antibodies, immunogenicity
Measure:Change in tumor volume
Time Frame:Weeks 6, 15, 24, 33, 42, 51, 60, 69, 78, 87, 96, 105
Safety Issue:
Description:Anti-tumor activity of MGD009 using both conventional RECIST 1.1 and immune-related RECIST criteria.

Details

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

Trial Keywords

  • B7-H3-expressing neoplasms

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