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

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

This study will evaluate the safety, tolerability and pharmacokinetics of CR011-vcMMAE in patients who have unresectable stage III or stage IV melanoma and have failed no more than 1 line of prior cytotoxic therapy. CR011-vcMMAE will be administered intravenously (IV) once every 3 weeks at escalating doses until the maximum tolerated dose (MTD) is reached. Once the MTD is defined, 18-32 patients will be enrolled to further evaluate the safety and efficacy of CR011-vcMMAE at this dose level. Additional dosing schedules of CR011-vcMMAE will also be explored.

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