Phase 1 study of CB-839, a small molecule inhibitor of glutaminase (GLS), alone and in combination with everolimus (E) in patients (pts) with renal cell cancer (RCC).

4568Background: CB-839 is a selective inhibitor of GLS, a key enzyme in the utilization of glutamine by many cancer cells. CB-839 has broad activity in preclinical models, including RCC where GLS is highly expressed. In RCC cell lines, CB-839 combines synergistically with E in vitro and in vivo, strongly inhibiting cell growth as well as glucose and glutamine metabolism. Previously reported data from this study have demonstrated that CB-839 achieved robust GLS inhibition in blood and tumors at well tolerated doses and that BID dosing with meals provided optimal PK and tolerability. Methods: CX-839-001 is an ongoing Phase 1 study evaluating the safety, PK, PD and efficacy of CB-839 in advanced/metastatic cancer patients. After completing an all-comers dose escalation of monotherapy CB-839, an RCC expansion cohort (n = 11) was opened to evaluate the efficacy of monotherapy CB-839 and was further expanded after achieving a preplanned overall response rate. In addition, the combination of CB-839 with standard...