This multicenter, open-label study will assess the safety and pharmacokinetics of DEDN6526A in patients with metastatic or unresectable melanoma. Cohorts of patients will receive escalating doses of DEDN6526A by intravenous infusion on Day 1 of each 21-day cycle. In the absence of disease progression or unacceptable toxicity, patients may continue to receive DEDN6552A for up to 17 cycles (1 year).

Inclusion Criteria:

• Adult patients, >/= 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Histologically confirmed metastatic melanoma (AJCC stage IV) or unresectable melanoma (AJCC Stage III)
• Prior failure of >/= 1 prior treatment regimens for metastatic or unresectable melanoma due to disease progression or unacceptable toxicity and for whom no standard therapy is available
• Measurable disease according to RECIST criteria
• Adequate bone marrow, liver and renal function
• Female patients of childbearing potential and male patients with female partners of childbearing potential must agree to use one highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception through the course of the study treatment and for 6 months after the last dose of study treatment

Exclusion Criteria:

• Treatment with cytotoxic or antibody based therapy within 21 days prior to first dose of study treatment, or with any other anti-cancer therapy within 5 half-lives of the therapy prior to first dose of study treatment
• Known active infection (including HIV and atypical mycobacterial disease, but excluding fungal infection of the nail beds)
• Current Grad >/= 2 toxicity (except alopecia or anorexia) from prior therapy
• Grade >/= 2 peripheral neuropathy
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapies (or recombinant antibody-related fusion proteins)
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• Untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control)
• Evidence of significant uncontrolled concomitant disease or disorder
• Pregnant or lactating women
• Prior treatment with any other antibody-drug conjugate (ADC) compound containing monomethyl auristatin E (MMAE) for the treatment of melanoma
• Previous participation in a clinical trial within 30 days of the day of first study drug administration (Cycle 1, Day 1)