Vibecotamab (previously XmAb14045) is a tumor-targeted antibody that contains both a CD123 binding domain and a cytotoxic T-cell binding domain (CD3). Xencor’s XmAb® Bispecific Fc Domain serves as the scaffold for these two antigen binding domains and confers long circulating half-life, stability and ease of manufacture on vibecotamab. CD123 is highly expressed on AML cells and leukemic stem cells and is associated with poorer prognosis in AML patients. Engagement of CD3 by vibecotamab activates T cells for highly potent and targeted killing of CD123-expressing tumor cells.
The structural stability and modularity enabled by the XmAb Bispecific Fc domain allowed the tuning of vibecotamab’s potency to balance anti-tumor activity with the reduction of immune toxicity that can result from T-cell activation.
In December 2020, updated data from the Phase 1 study of vibecotamab in patients with relapsed or refractory AML were presented at the American Society of Hematology (ASH) Annual Meeting. The efficacy analysis included evaluable patients who received a dose of at least 0.75 mcg/kg, completed at least the first cycle of treatment and had at least one post-treatment disease assessment. Clinical responses were associated with lower baseline disease burden, indicated by patients with lower blast percentages and lower PD1 expression on CD8+ and CD4+ T cells. Seven out of eight patients with responses had a baseline blast count less than or equal to 25% blasts in bone marrow. The objective response rate was 26% (7/27) when using this threshold to define the population with low disease burden for the analyses.