686 Mechanism of action of LAVA-051, a bispecific Vγ9Vδ2 T-cell engager (bsTCE), confirmed in the clinical setting

Background LAVA-051, a CD1d-targeting first-in-class bispecific single domain antibody (27 kDa), was brought into the clinic based on its high potency antitumor activity through dual engagement of V g 9V d 2-T and iNKT cells, and a low risk of cytokine release syndrome (CRS). Methods A phase 1 study using LAVA-051 is ongoing in patients with relapsed/refractory MM or CLL to determine the recommended phase 2 dose (RP2D). This study has been approved by relevant ethics committees (NCT04887259). A panel of specific pharmacodynamic assays is included to determine the pattern of change in the binding of LAVA-051 to patients ’ peripheral blood V g 9V d 2-T cells (i.e. V g 9V d 2-TCR occupancy) and in the frequency and activation status of V g 9V d 2-T and iNKT cells in circulation. Data presented are focused on the comparison of clinical to pre-clinical observations. Results LAVA-051 triggers V g 9V d 2-T and iNKT cell mediated pro-inflammatory cytokine production, proliferation and antitumor activity in in vitro and ex vivo assays