Calithera Biosciences, an American pharmaceutical company focused on developing drugs for the treatment of cancer, has announced the initiation of a randomised phase 2 clinical trial of CB-839, a glutaminase inhibitor, combined with everolimus (Afinitor)‎ in patients with clear cell renal cell carcinoma (RCC).

Many cancers are dependent on the nutrient glutamine for growth and survival. CB-839 blocks the actions of glutaminase, an enzyme needed by cancer cells to use glutamine effectively, thereby interfering with tumour growth. Most patients with clear cell RCC lack the tumour suppressor gene VHL, making the cancer cells more dependent on glutamine due to a loss of ability to make fatty acids from glucose.  Since the mTOR inhibitor everolimus blocks the use of glucose by cancer cells, the combination of CB-839 with everolimus has a dual action to stop tumour growth in clear cell RCC.

“Despite the advances in the treatment of renal cell carcinoma, there remains significant unmet need for patients who have progressed following treatment with an anti-PD1 and/or tyrosine kinase inhibitors,” said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera.  “The initiation of this study marks an important milestone for our company, as it is the first randomised trial of CB-839…..”.  The US Food and Drug Administration (FDA) has granted fast track designation to CB-839 for the treatment of RCC in recognition of the lack of treatment options available to patients.

The phase 2 clinical trial is a randomised, double-blind, placebo controlled trial to evaluate the safety and efficacy of CB-839 in combination with everolimus versus placebo with everolimus in approximately 250 people with metastatic, clear cell RCC. Patient will have previously received at least two lines of drug treatment for advanced RCC, including a VEGFR-targeted tyrosine kinase inhibitor, such as sunitinib or pazopanib, and at least one of either cabozantinib (Cabometyx) or an active PD-1/PD-L1 inhibitor, such as nivolumab. Patients will be randomised in a 2:1 ratio.  The primary endpoint is progression free survival (PFS), while overall survival (OS) will be assessed as a secondary endpoint. The trial will be conducted at multiple sites in the United States, Europe and Canada, and some of the sites in the US are now recruiting patients.

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