Entered into a Phase 1 clinical study, as monotherapy and in combination with pembrolizumab, for the treatment of patients with in subjects with select advanced solid tumors in May 2019.

Tumor infiltrating lymphocytes express multiple immune checkpoints and co-stimulatory receptors. Xencor’s bispecific tumor microenvironment (TME) activators seek to more effectively reactivate these tumor-killing T cells by engaging multiple T-cell targets simultaneously. This approach eliminates the need for the multiple antibodies, and it allows for more selective targeting of T cells with high checkpoint expression, which may potentially improve the therapeutic index of combination immunotherapies.

XmAb841 (XmAb22841) is a bispecific antibody that simultaneously targets immune checkpoint receptors CTLA-4 and LAG-3 and is designed to promote tumor-selective T-cell activation. 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. XmAb bispecific Fc domains have been engineered to eliminate Fc gamma receptor (FcγR) binding, with the intent to prevent activation and/or depletion of T cells via engagement by FcγR-expressing cells. In preclinical studies, the blockade of CTLA-4 and LAG-3, with XmAb841, and PD-1, with an anti-PD1 antibody, significantly enhanced T cell proliferation and activation, and anti-tumor activity in vivo.

Each of Xencor’s three bispecific TME activators tests a distinct mechanism of TME activation. XmAb717 and XmAb104 are also being evaluated in Phase 1 clinical studies.