A Study of DFRF4539A in Patients With Relapsed or Refractory Multiple Myeloma

• Safety: Incidence of adverse events [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
• Safety: Maximum tolerated dose/dose-limiting toxicities [ Time Frame: approximately 6 months ] [ Designated as safety issue: No ]

• Immunogenicity: Serum antitherapeutic antibody levels [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
• Pharmacokinetics: Area under the concentration - time curve (AUC) [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
• Objective response, tumor assessments according to International Myeloma Working Group (IMWG) Uniform Response Criteria and/or European Bone Marrow Transplant (EBMT) Criteria [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
• Duration of objective response, defined as time from first documented objective response to progression or death of any cause [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
• Progression-free survival, defined as time from first study treatment (Cycle 1, Day 1) to disease progression or death during study or within 30 days after last dose of study drug, whichever occurs first [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]

This multicenter, open-label study, dose-escalating study will assess the safety and efficacy of DFRF4539A in patients with relapsed or refractory multiple myeloma. Cohorts of patients will receive multiple ascending doses of intravenous DFRF4539A, for up to eight 3-week cycles. Patients exhibiting acceptable safety and evidence of clinical benefit may receive up to eight further cycles of DFRF4539A. Anticipated time on study treatment is 1 year or until disease progression or unacceptable toxicity occurs.

Inclusion Criteria:

• Adult patients; >/= 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
• Relapsed or refractory multiple myeloma for which no effective standard therapy exists
• One of the prior therapies must have included a proteosome inhibitor or an immunomodulatory drug
• Measurable disease as defined by protocol

Exclusion Criteria:

• Prior use of monoclonal antibody within 4 weeks before Cycle 1, Day 1
• Treatment with radiotherapy, thalidomide, lenalidomide, bortezomib, any chemotherapeutic agent, or treatment with any investigational anti-cancer agent within 2 weeks prior to Cycle 1, Day 1
• Toxicities from any previous treatment must be resolved prior to Cycle 1, Day 1, except for neuropathy
• Completion of autologous stem cell transplant within 100 days prior to Cycle 1, Day 1
• Prior allogeneic stem cell transplant
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
• Grade > 2 peripheral neuropathy
• Active infection at screening or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks prior to Cycle 1, Day 1
• Positive for hepatitis B, hepatitis C or HIV infection
• Pregnant or lactating women