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Cell metabolism in kidney cancer tumours is disrupted, and tumour cells tend to have high levels of an enzyme called glutaminase. Glutaminase is a key enzyme in the metabolism of glutamine, which is important for tumour growth and survival. Glutamine is an amino acid that is found in most proteins. Kidney cancer cells have increased dependence on glutamine for cell growth. Telaglenastat is a glutaminase inhibitor that blocks the use of glutamine by kidney cancer cells as a vital source of energy for cell growth. In a phase 1 study, telaglenastat showed encouraging safety and effectiveness when used in combination with cabozantinib as a second- or third-line treatment for metaststic kidney cancer.
The phase 2 CANTATA study compared telaglenastat plus cabozantinib with placebo plus cabozantinib in previously treated patients with clear-cell metastatic kidney cancer. There were 444 patients randomly put into two groups to be treated with telaglenastat/cabozantinib or placebo/cabozantinib. Patients were followed for an average of around 1 year. There was no benefit of telaglenastat/cabozantinib in terms of time to when the drug stopped working and the cancer started growing again (9.2 versus 9.3 months), or a reduction in the size of the cancer (31% versus 28%) compared to placebo/cabozantinib. Rates of side effects were similar between the two treatment groups and included high blood pressure and diarrhoea.
In summary, the addition of telaglenastat did not improve the efficacy of cabozantinib as a second or third-line treatment for metastatic kidney cancer. However, the combination of telaglenastat plus cabozantinib was well tolerated with side effects expected from each treatment.