AT9283 in Combination with Lenalidomide Results in Synergistic Anti-Myeloma Activity

Researchers from the Massachusetts General Hospital Cancer Center, Harvard Medical School and the Dana-Farber Cancer Institute, in Boston, MA, have evaluated the activity of Astex’s multi-targeted kinase inhibitor, AT9283, in combination with established multiple myeloma drugs and found a strong synergistic effect when AT9283 was combined with lenalidomide. The synergistic effect is thought to be due to the fact that the two drugs target different pathways and different phases of the cell cycle, thus augmenting their individual anti-myeloma activities. The results of the study provide a rationale for the clinical evaluation of AT9283 in combination with lenalidomide in multiple myeloma patients.

AT9283 Suppresses Tumor Growth in Aggressive B-Cell Non-Hodgkin’s Lymphoma

Researchers from the Arizona Cancer Center will present data from a study to examine whether targeting inhibition of mitosis with AT9283 would be effective in promoting apoptosis in aggressive B-Cell Non Hodgkin’s Lymphoma cell lines. The study demonstrated that the combination of AT9283 plus docetaxel resulted in a statistically significant level of tumor growth inhibition over controls at well tolerated doses. These results suggest that AT9283 plus docetaxel may represent a novel therapeutic strategy for patients with aggressive B-Cell Non Hodgkin’s Lymphoma.

AT9283 Biomarker Strategy in Paediatric Patients

The presentation focused on the development of a biomarker to support the forthcoming Cancer Research UK Drug Development Office-sponsored Phase I trial for AT9283 in paediatric and adolescent patients with leukaemia. By adapting and validating a Plasma Inhibitory Activity (PIA) assay to detect inhibition of Aurora, ABL and FLT3 kinases, a method for the non-invasive assessment of the pharmacodynamic action of AT9283 has been developed that can easily be adapted to paediatric patients for whom limited volumes of blood are available for such studies. The PIA assay, which may help delineate important mechanisms of action for novel anti-leukaemic drugs, will be used to assess target kinase modulation in a Phase I trial of AT9283 in children and adolescents with relapsed and refractory acute leukaemia. This work is being conducted by a team at The Institute of Cancer Research in Sutton, UK, with funding from Cancer Research UK.