A new drug that targets a key enzyme that cancer cells need to keep them alive has been shown to be effective at controlling clear cell and papillary renal cell carcinoma (RCC) when given in combination with the mTOR inhibitor, everolimus.
The results from a phase I clinical trial with the new drug, CB-839, were presented at the 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Munich, Germany, last week. Of 15 patients with clear cell and papillary RCC who had been given CB-839 together with everolimus, 93% had their tumour controlled by the regimen: the tumour shrank by more than 30% in one patient (called a partial response), was stable in 13 other patients (stable disease), and grew by more than 20% in the last patient (called progressive disease).
CB-839 targets an enzyme called glutaminase, which is involved in the conversion of glutamine to glutamate. Glutamate is an important nutrient for cancer cells – without it they die. In the laboratory, CB-839 has been shown to be effective at inhibiting glutaminase in renal cell cancers, and enhancing the anti-tumour efficacy of everolimus. “These results suggest that CB-839 is a very tolerable drug with significant potential in combination therapy for kidney cancer patients,” said Dr Meric-Bernstam, chair of the Department of Investigational Cancer Therapeutics and Medical Director of the Institute of Personalized Cancer Therapy at the University of Texas MD Anderson Cancer Centre (USA).
CB-839 is being developed by Calithera Biosciences, a clinical-stage American pharmaceutical company focused on discovering and developing novel small molecule drugs directed against tumour metabolism and tumour immunology targets for the treatment of cancer.