LAVA Therapeutics N.V. (NASDAQ: LVTX) has announced the dosing of the first patient in its Phase 1 clinical trial of LAVA-1266, a bispecific gamma delta T cell engager, for the treatment of hematological cancers. The study, currently underway in Australia, is evaluating LAVA-1266 in adult patients with CD123-expressing acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). This first-in-human trial marks a significant step for LAVA's proprietary Gammabody® platform.
LAVA-1266: A Novel Approach to Targeting CD123
LAVA-1266 is a potent and selective bispecific anti-CD123 Gammabody® designed to lyse CD123+ tumor cells with high potency while minimizing off-target effects. The drug works by engaging Vγ9Vδ2-T cells to target and kill CD123-expressing cancer cells. Preclinical studies have demonstrated that LAVA-1266 preferentially targets and kills CD123+ cells and induces Vγ9Vδ2-T cell activation.
According to Stephen Hurly, President and Chief Executive Officer of LAVA Therapeutics, preclinical models have shown tumor cell lysis with limited off-target effects, suggesting LAVA-1266 has the potential to be a safe and effective treatment for AML and MDS.
Overcoming Limitations of Previous Therapies
CD123 is a well-recognized therapeutic target for AML, but earlier generations of CD123-targeted therapies have been limited by on-target, off-tumor toxicity, cytokine release syndrome, and capillary leak syndrome. LAVA-1266 aims to address these limitations through its unique design.
Charles Morris, MD, Chief Medical Officer of LAVA Therapeutics, expressed enthusiasm for LAVA-1266, citing its strong preclinical profile and the company's anticipation of working with clinical study sites in Australia. Preclinical data suggests that treatment with LAVA-1266 produces high levels of specific tumor cell lysis, with substantially less cytokine release compared to CD3-based T cell engagers, and increased survival in an AML xenograft model, without the co-activation of immunosuppressive regulatory T cells.
Trial Design and Objectives
The open-label, multi-center Phase 1 study (ACTRN12624001214527) is enrolling approximately 50 adults with CD123+ relapsed/refractory AML and certain grades of MDS (intermediate risk, high risk, or extremely high risk). Patients will be dosed every two weeks (Q2W), with an initial target dose of 100 μg for the first cohort. The primary objectives of the study are to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary anti-tumor activity of LAVA-1266.
Initial Phase 1 data read-out is expected by the end of 2025. This trial represents a crucial step in LAVA Therapeutics' mission to develop innovative immunotherapies for hematologic malignancies and solid tumors, leveraging its Gammabody® platform to harness the power of gamma-delta T cells in cancer treatment. LAVA's pipeline includes three internal and partnered clinical-stage bispecific gamma-delta T cell engagers for the treatment of solid tumor and hematological cancers including LAVA 1266, targeting CD123+ cancers; PF-08046052, targeting EGFR; and JNJ-89853413, targeting hematological cancers. The pipeline also includes preclinical programs.
