Calithera Biosciences presents data from randomized Phase 2 ENTRATA study
Calithera Biosciences presented supporting data for its previously reported positive results from its randomized placebo-controlled Phase 2 ENTRATA study of telaglenastat in combination with everolimus in patients with advanced renal cell carcinoma. The telaglenastat-everolimus combination doubled the median progression-free survival in heavily pre-treated patients with advanced RCC and had a well-tolerated safety profile. Telaglenastat is the first glutaminase inhibitor to demonstrate clinical activity for the treatment of cancer. Calithera announced top-line results from the ENTRATA trial in June. Key demographics in patients enrolled in the phase 2 ENTRATA study were balanced between the two treatment arms and were heavily pre-treated, with a median of three prior lines of therapy for advanced metastatic disease including 70% with two or more prior tyrosine kinase inhibitors, and 68% with intermediate/poor MSKCC prognostic score. 88% of patients received prior PD-1/PD-L1 therapy. When added to everolimus, telaglenastat doubled the median PFS to 3.8 months as compared to 1.9 months for everolimus alone and reduced the risk of disease progression or death by 36%. The primary endpoint of the trial was PFS per investigator assessment with a predetermined threshold of less than or equal to 0.2 one-sided. Overall response per Response Evaluation Criteria in Solid Tumors version 1.1 was 2.2% vs. 0%, and stable disease was 56.5% vs. 47.8%. The secondary endpoint of overall survival is not yet mature. Frequency of all-grade adverse events in the telaglenastat-containing arm were comparable to that of everolimus alone. Grade 3 or higher adverse events occurred in 80.4% of patients in the telaglenastat plus everolimus arm versus 60.9% in the everolimus plus placebo arm. Adverse events leading to discontinuation of any study drug were comparable. The ENTRATA trial is a randomized, double-blind Phase 2 trial designed to evaluate the efficacy and safety of telaglenastat in combination with everolimus versus placebo with everolimus in patients with advanced clear cell RCC who have been treated with at least two prior lines of systemic therapy, including at least one VEGFR-targeted TKI. Patients were randomized in a 2:1 ratio, and stratified by prior TKI treatment and MSKCC prognostic score. The trial enrolled 69 patients at multiple centers in the U.S. Telaglenastat is also being investigated in the CANTATA trial, a global, randomized, double-blind trial designed to evaluate the efficacy and safety of telaglenastat in combination with cabozantinib versus placebo with cabozantinib in patients with advanced or metastatic RCC who have been treated with one or two prior lines of systemic therapy including at least one vascular endothelial growth factor tyrosine kinase inhibitor or the combination of nivolumab and ipilimumab. In April 2018, the U.S. Food and Drug Administration granted Fast Track designation to telaglenastat in this indication. The primary endpoint is progression-free survival by blinded independent review, and a key secondary endpoint is overall survival. Calithera plans to report top-line efficacy and safety data from the trial in the second half of 2020.