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Acute myeloid leukemia (AML) is a disease with high unmet medical need. Standard induction chemotherapy can lead to complete remission in patients with a favorable genetic risk profile; however, about half of patients are ineligible for this intensive regimen. In those patients with a non-favorable genetic risk profile, the preferred treatment strategy is allogeneic stem cell transfer, but the majority of patients are ineligible due to age and other comorbidities.

Introduction:Multiple myeloma (MM) is a highly prevalent hematological malignancy, with a worldwide incidence of over 62,000 patients in 2012. Despite significant progress in the development of MM treatments in the last decade, there is a great unmet medical need for MM patients who relapse on existing therapies. Given the greater time needed for relapses to manifest when minimal residual disease (MRD) is reduced, new therapies should be aimed at eliminating MRD. Bispecific T cell engager (BiTE®) molecules recruit T cells to cancer cells and trigger T cell-dependent cellular cytotoxicity (TDCC). BiTEs are clinically validated for the treatment of hematological malignancies and have the potential to greatly reduce MRD. CD38 is a membrane protein normally expressed by plasma cells, lymphocytes, and other immune cells and is a clinically validated tumor-associated antigen expressed at high levels on MM cells. Herein, we describe for the first time AMG 424, a novel, humanized T cell-recruiting bispecific anti-CD3/CD38 antibody containing an XmAb® Fc domain that cross-reacts with nonhuman primate (NHP) CD3 and CD38. AMG 424 was selected for its affinity for CD3 and CD38 in an effort to overcome the challenges associated with CD38 and CD3 binding.