The addition of the glutaminase inhibitor telaglenastat to cabozantinib did not improve the efficacy of cabozantinib in patients with metastatic clear cell renal cell carcinoma (RCC), according to results of the CANTATA study.
“Based on the well-established characterization of RCC as a highly metabolic cancer, recent studies have pointed to glutamine metabolism as a promising therapeutic target,” study researchers wrote. “Telaglenastat is an investigational, oral, selective, and potent glutaminase inhibitor that has been evaluated preclinically and clinically for the treatment of solid and hematologic cancers…Preclinical studies have shown RCC models to be highly susceptible to telaglenastat when combined with other anticancer agents.”
CANTATA was a double-blind study that randomly assigned 444 patients with metastatic clear-cell RCC who had progressed on one to two prior lines of therapy to oral cabozantinib with telaglenastat (800 mg twice daily) or placebo.
At a median follow-up of 11.7 months, the median progression-free survival was 9.2 months for combination treatment compared with 9.3 months for cabozantinib alone.
“Among the possible explanations for the lack of efficacy of telaglenastat in CANTATA is the possibility of insufficient exposure to telaglenastat,” the researchers wrote. “However, the 800-mg twice-daily dose was established based on the analysis of pharmacokinetics/pharmacodynamics from prior phase 1 studies, including the demonstration of strong glutaminase inhibition in platelets and tumors at the 600-mg twice-daily and 800-mg twice-daily dose.”
Overall response rate was 31% for telaglenastat plus cabozantinib compared with 28% for cabozantinib alone. Two patients in each arm had a complete response.
Although overall survival data were not mature at the time of data cutoff, preliminary data shown no difference between the study arms.
“We believe that CANTATA provides valuable insight into efficacy outcomes of a contemporary population of patients with metastatic RCC who receive cabozantinib in the second-line or third-line setting,” the researchers wrote. “While the addition of telaglenastat to cabozantinib did not improve outcomes in this unselected RCC patient population, future studies of telaglenastat may be warranted to determine the effect of glutaminase inhibition in biomarker-driven patient populations with high dependence on glutamine/glutaminase, and/or in combination with other therapeutic partners.”