LAVA Therapeutics N.V. announced a poster presentation highlighting updated data, including safety, pharmacodynamics (PD) and pharmacokinetics (PK) from the ongoing Phase 1/2a clinical trial of LAVA-051 in patients with relapsing/refractory (R/R) chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) at the 64thAmerican Society of Hematology (ASH) Annual Meeting and Exposition, taking place in New Orleans, Louisiana and virtually December 10–13, 2022. The presentation includes initial data from patients receiving LAVA-051 subcutaneously, along with updates on the intravenous dosing-cohorts. In addition to the favorable safety profile demonstrated as of the data cutoff (November 11, 2022), LAVA-051 showed predictable and linear pharmacokinetics and on-mechanism pharmacodynamic parameters consistent with V?9Vd2-T cell engagement, including increasing occupancy of patient V?9Vd2-T cells with LAVA-051 and consistent increases in the expression of T-cell activation markers.

Moreover, potential signs of clinical activity of LAVA-051 were seen. LAVA-051 is a humanized Gammabody™ designed to activate both V?9Vd2 (Vgamma9 Vdelta2) T cells and type 1 NKT cells to kill CD1d-expressing tumor cells. LAVA-051 consists of two single domain antibodies linked via a short five amino acid glycine-serine linker.

One domain antibody recognizes the Vd2 chain of the V?9Vd2 T cell receptor, and the other domain antibody is specific for CD1d, a glycoprotein involved in the presentation of (glyco)lipid antigens to distinct T cell populations including type 1 NKT cells, that can be expressed on a wide range of hematologic malignancies, including chronic lymphocytic leukemia, multiple myeloma, and acute myeloid leukemia.