LAVA Begins Phase 1 LAVA-1266 Trial in Blood Cancer Patients

UTRECHT, The Netherlands, and PHILADELPHIA, PA, USA, January 10, 2025 – LAVA Therapeutics N.V., a clinical-stage company specializing in immuno-oncology, announced a milestone with the administration of the first dose to a patient in its Phase 1, first-in-human study of LAVA-1266. This investigational treatment is being developed for hematologic cancers, specifically acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). LAVA-1266 is part of the company's Gammabody® platform, which is known for its bispecific gamma delta T cell engagers targeting CD123.

Stephen Hurly, the President and CEO of LAVA Therapeutics, expressed enthusiasm about the commencement of patient dosing with LAVA-1266. He emphasized the promising results from preclinical trials, which demonstrated efficient tumor cell destruction with minimal collateral effects. These findings reinforce the potential of LAVA-1266 as a viable treatment option for AML and MDS. The company plans to thoroughly assess the safety, pharmacokinetics, and pharmacodynamics of LAVA-1266, aiming to deliver preliminary outcomes from the dose-escalation phase by the year's end.

Charles Morris, Chief Medical Officer of LAVA, highlighted CD123 as an important therapeutic target for AML. Previous therapies targeting CD123 faced challenges due to adverse effects like on-target, off-tumor toxicity and syndromes such as cytokine release and capillary leak. Morris noted that LAVA-1266's robust preclinical profile presents a favorable prospect, and the company is eager to collaborate with clinical sites in Australia to advance this research.

LAVA-1266 is a potent bispecific T cell engager (bsTCE) developed to target and destroy CD123+ tumor cells by engaging Vγ9Vδ2 T cells via LAVA’s Gammabody® platform. The bsTCE aims to provide high efficacy and a broad therapeutic range. Preclinical investigations confirmed the expression of CD123 and the presence of Vγ9Vδ2 T cells in AML patient samples. LAVA's studies demonstrated that LAVA-1266 effectively targets and eradicates CD123+ cells, activating Vγ9Vδ2 T cells. It also achieved high levels of specific tumor cell destruction with lower cytokine release compared to CD3-based T cell engagers, enhancing survival rates in an AML xenograft model without activating immunosuppressive regulatory T cells.

The ongoing Phase 1 trial of LAVA-1266 is an open-label, multi-center study being conducted in Australia. It includes dose escalation and expansion stages, assessing LAVA-1266 in approximately 50 adults with CD123+ relapsed or refractory AML and certain high-risk categories of MDS. Participants receive doses bi-weekly, starting with a target dose of 100 µg for the initial cohort. The study aims to evaluate the treatment's safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary anti-tumor effects.

LAVA Therapeutics is dedicated to advancing its Gammabody® platform to create a range of bispecific gamma-delta T cell engagers targeting both solid tumors and hematologic cancers. The company's pipeline includes multiple clinical-stage bispecific gamma-delta T cell engagers, such as LAVA-1266 targeting CD123+ cancers, as well as PF-08046052 and JNJ-89853413, which target EGFR and hematological cancers, respectively. Additional preclinical programs are also in development.