Perlmutter Cancer Center

B7-H6 is expressed in several tumor types and does not appear to be appreciably expressed in normal tissue. BI 765049 is a novel IgG-like T cell engager. The activity of BI 765049 requires simultaneous binding to B7-H6-expressing target cells and T cells; the resulting proximity and formation of the cytolytic synapse triggers T cell mediated redirected lysis of B7-H6-expressing target cells. As a result of the formation of the cytolytic synapse the target cells undergo apoptosis; subsequently the T cells are activated, start to proliferate locally and produce cytokines and chemokines, which is expected to result in reduced tumor burden and to halt or slow down disease progression in patients. Consistent with the mode of action of T cell engagers, treatment is expected to subsequently lead to up-regulation of programed cell death-1 (PD-1) on T cells and increased expression of programed cell death ligand-1 (PD-L1) on tumor cells. Upregulation and activation of PD-1/PD-L1 axis may reduce activity of BI 765049 as a single agent and constitutes the rationale for combination with the anti-PD-1 antibody ezabenlimab. Preclinical data support testing BI 765049 in humans with the objective to improve the outcome of patients with B7-H6 positive tumors. This open-label, dose-escalation trial represents the first protocol for BI 765049 treatment in humans. Results on safety, doses, administration regimen, pharmacokinetics (PK), and pharmacodynamics (PDc), as well as preliminary antitumor activity, acquired in this trial will provide the basis for further development of BI 765049.