Efficacy Study of Pharmacokinetic(PK)/Pharmacodynamic(PD) Relationship of Monotherapy MORAb-004 in Metastatic Melanoma
Condition: Metastatic Melanoma
MeSH terms: Melanoma
Intervention: MORAb-004 (monoclonal antibody)
Intervention description: Subjects will receive one cycle of treatment with MORAb-004, administered intravenously, on Days 1, 8, 15, and 22 (4 administrations per cycle). Additional cycles will continue without interruption until disease progression occurs or clinical or symptomatic progression as suggested by an investigator.
Intervention MeSH terms: Antibodies; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 76.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: melanoma; malignant; metastatic

Summary:

      This is a global, Phase 2, open label, dose selection, proof-of-concept study to assess
      progression free survival in subjects with metastatic melanoma.

      Approximately 80 subjects at 29 sites in the U.S., U.K., Germany and Australia will be
      randomized into one of two dose groups: 2 mg/kg, 4 mg/kg. Weekly treatment will continue
      until disease progression.

      Subjects must have measurable disease by CT Scan or MRI and must have completed at least one
      prior round of chemotherapy.

      Subjects will be assessed for Efficacy, PK/PD, Overall survival, and Safety (Adverse
      Events/Adverse Events of Interest, Electrocardiograms (ECG's), clinical labs, physical
      exams/vital signs, tolerability).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Be surgically sterile or consent to use a medically acceptable method of contraception
             throughout the study period.

          -  Histologically confirmed diagnosis of metastatic melanoma

          -  At least 1 prior systemic treatment for metastatic melanoma with disease progression
             following treatment

          -  Measurable disease, as defined by RECIST v1.1, assessed within 4 weeks prior to study
             entry

          -  At least 3 week interval between first infusion of test article and most recent prior
             systemic anticancer therapy. All treatment-associated toxicity must be resolved to
             less than or equal to Grade 1 before the administration of MORAb-004

          -  Have a life expectancy of at least 3 months as estimated by the investigator

          -  Have other significant medical conditions well-controlled and stable, in the opinion
             of the investigator, for at least 30 days prior to Study Day 1

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          -  Have sites of disease amenable to the protocol-specified biopsy (Note: All
             participants will have protocol-specified biopsy at Screening. The second,
             on-treatment biopsy will be mandatory in the first 30 randomized participants only.
             For all other participants, the second biopsy is optional.

          -  Laboratory tests results prior to Study Day 1 within limits as outlined in protocol

        Exclusion Criteria:

          -  Have received no prior systemic treatment for metastatic melanoma

          -  Evidence of other active malignancy requiring treatment within the last 5 years (other
             than basal cell or squamous cell carcinoma of the skin), or active brain metastasis

          -  Clinically significant heart disease (Congestive heart failure of New York Heart
             Association [NYHA] Class 3 or 4, angina not well controlled by medication, or
             myocardial infarction within 6 mos.), or ECGs demonstrating clinically significant
             arrhythmias

          -  Have any other serious systemic disease, including active bacterial or fungal
             infection, or any medical condition requiring cytotoxic therapy or chronic (at least 4
             consecutive weeks) systemic corticosteroid use

          -  Have active viral hepatitis or symptomatic Human immunodeficiency virus (HIV)
             infection

          -  Be breast-feeding, pregnant, or likely to become pregnant during the study

          -  Known allergic reaction to a prior monoclonal antibody therapy

          -  Previous treatment with MORAb-004

          -  Brain metastasis