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Telaglenastat Plus Everolimus Improves PFS vs Placebo Plus Everolimus in Metastatic Renal Cell Carcinoma
In a phase 2 study, telaglenastat, an oral glutaminase inhibitor, plus everolimus, an mTOR inhibitor, improved progression-free survival (PFS) in patients with metastatic renal cell carcinoma (RCC) who had previously been treated with tyrosine kinase inhibitors (TKIs) and checkpoint inhibitors, when compared to placebo plus everolimus.
The phase 2 ENTRATA trial enrolled 69 patients with advanced or metastatic RCC who had previously been treated with at least 2 lines of therapy between September 6, 2017 and May 11, 2020. All patients had previously experienced treatment with at least 1 vascular endothelial growth factor receptor (VEGFR)-targeted TKI, and 88% had previously experienced treatment with checkpoint inhibitors.
Patients were randomized in a 2:1 ratio to receive everolimus daily plus either telaglenastat (n = 46) or placebo (n = 23) twice daily, in 28-day cycles. Treatment continued until disease progression or unacceptable toxicity. The primary outcome of the study was PFS, and the secondary outcome was overall survival (OS).
With a median follow-up duration of 7.5 months, the median PFS for the telaglenastat arm was 3.8 months compared to 1.9 months for the placebo arm (hazard ratio, 0.62; 95% confidence interval, 0.34 to 1.20; one-sided P = .079). In the telaglenastat group, there was 1 patient with a partial response, and 26 patients with stable disease. In the placebo arm, there were 11 patients with stable disease.
Treatment-emergent adverse events included fatigue, anemia, cough, dyspnea, elevated serum creatinine, and diarrhea. Among patients treated with telaglenastat, 74% developed grade 3/4 adverse events vs 61% of patients treated with placebo.
Source:
Lee CH, Motzer R, Emamekhoo H, et al. Telaglenastat plus everolimus in advanced renal cell carcinoma: A randomized, double-blinded, placebo-controlled, phase II ENTRATA trial. Clin Cancer Res. Published online June 23, 2022. doi:10.1158/1078-0432.CCR-22-0061
