Efficacy Study of Pharmacokinetic(PK)/Pharmacodynamic(PD) Relationship of Monotherapy MORAb-004 in Metastatic Melanoma

A Study of the Efficacy and PK/PD Relationship of Monotherapy MORAb-004 in Subjects With Metastatic Melanoma

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).

MORAb-004 is a monoclonal antibody directed against endosialin, a cell surface glycoprotein, which is expressed on cells involved in tumor vasculature. Studies have found endosialin to play a key role in tumor growth and neovessel formation in numerous cancer types including melanoma. Preclinical pharmacological studies have shown that MORAb-004 is a potentially useful anti-cancer agent. This clinical trial is being performed to determine the efficacy of MORAb-004 at two dose levels in subjects with metastatic melanoma, as well as to establish serum pharmacokinetics and pharmacodynamics of the antibody.

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