Calithera Biosciences announced earlier this week that the US Food and Drug Administration (FDA) has granted fast track designation to CB-839 for use in combination with cabozantinib for the treatment of patients with metastatic renal cell carcinoma (RCC) who received one or two prior courses of treatment (including at least one TKI).
Fast track designation by the FDA expedites the review process to facilitate development of drugs which treat a serious or life-threatening condition and fill an unmet medical need.
CB-839 is a first-in-class, oral, selective, potent glutaminase inhibitor. Genetic changes in the metabolic pathways of tumours often cause a dramatic rise in the uptake of the nutrients glucose and glutamine. Removal of glutamine leads to a substantial reduction in cell growth or induces cell death in certain types of cancer cells, indicating that these cells are dependent on, or “addicted” to, glutamine. Normal cells do not show this pronounced dependence on glutamine. The enzyme glutaminase, which converts glutamine to glutamate, has been identified as critical in the use of glutamine by cancer cells. CB-839 blocks glutaminase and prevents cancer cells from being able to use glutamine, potentially leading to reduced tumour cell growth and/or cell death.
CB-839 is being assessed in the CANTATA trial, which is a randomised double-blind clinical study of cabozantinib in combination with CB-839 or placebo in 298 patients with clear cell RCC. The primary endpoint is progression free survival. The study is currently recruiting patients.
Susan Molineaux, Ph.D., president and CEO of Calithera, added:
“Despite a number of new therapies for the treatment of renal cell carcinoma, there remains a significant unmet need among advanced patients who have received prior treatment. We are pleased that CB-839 has been granted Fast Track designation, demonstrating the FDA’s commitment to facilitate the development and expedite the review of our glutaminase inhibitor as an important new therapy for patients with advanced or metastatic renal cell carcinoma who have failed prior systemic therapy.”