A Phase I/II Study of CR011-vcMMAE in Subjects With Unresectable Stage III or Stage IV Melanoma

Inclusion Criteria:

- Male or female with age ≥ 18 years.

- Progressive or new metastatic melanoma, stage III or IV.

- Measurable disease by CT / MRI

- Failure of no more than 1 line of prior cytotoxic therapy.

- Adequate bone marrow, renal and hepatic function

- Leukocytes ≥ 3000/mm3, ANC ≥ 1,500 cells/mm3, Platelets ≥ 100,000/mm3

- Hemoglobin ≥ 10 g/dL (transfusion allowed)

- Total bilirubin ≤ 1.5 x upper normal limit (UNL)

- AST (SGOT), ALT (SGPT) ≤ 3.0 x UNL (≤ 5.0 x UNL may be acceptable)

- Serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance > 45 mL/min/1.73
m2

- PT/aPTT < 1.5 x UNL or within therapeutic range via anti-coagulation therapy

- Karnofsky PS ≥ 70%.

- Estimated life expectancy > 3 months.

- Signed informed consent approved IRB and ability to comply with the study or
monitoring procedures.

- Subjects with evaluable disease are eligible in dose-escalation cohorts

Exclusion Criteria:

- Prior therapies for disease under study less than 4 weeks prior to enrollment.

- Major surgery or trauma within 4 weeks of enrollment.

- Active brain metastases

- Active chronic inflammatory, autoimmunity, immunodeficiency disease, and vascular or
hemorrhagic disorders.

- History of allergic reactions to dolastatin, auristatin or compounds of similar
composition.

- Significant cardiovascular disease

- Other malignancies

- Pregnancy or breast feeding

- Refusal or inability to use effective means of contraception (for men, and women with
childbearing potential)

- History of or test-positive to HIV, or hepatitis B or C