telaglenastat + everolimus

A combination therapy comprising **telaglenastat**, a selective oral glutaminase inhibitor, and **everolimus**, an oral mTOR inhibitor. This combination is under investigation primarily for **advanced or metastatic renal cell carcinoma (RCC)**, particularly in patients who have previously received treatment with tyrosine kinase inhibitors and checkpoint inhibitors. **Telaglenastat** targets glutaminase, blocking glutamine metabolism that supports cancer cell growth, while **everolimus** inhibits the mechanistic target of rapamycin (mTOR), a kinase involved in cell proliferation and survival. The combination aims to synergistically suppress tumor cell metabolism (both glutamine and glucose pathways), resulting in anti-tumor activity seen in both preclinical and clinical settings. The best-studied clinical trial to date is the phase 2 ENTRATA trial, which showed increased progression-free survival versus everolimus alone in heavily pretreated advanced RCC patients. Common adverse effects included fatigue, anemia, cough, dyspnea, elevated serum creatinine, and diarrhea. Severe or life-threatening adverse events were more frequent in the combination group but manageable[1][2][3][4][5].

Brand names

Afinitor (for everolimus)CB-839 (development code for telaglenastat)

Other names

TelaE