Telaglenastat is an investigational drug, currently undergoing scientific study to determine its safety and effectiveness. It is being explored for its potential to address certain diseases.
What Telaglenastat Is
Telaglenastat, also known as CB-839, is a small molecule, oral allosteric inhibitor of glutaminase (GLS). Glutaminase is an enzyme that metabolizes glutamine, an amino acid many rapidly growing cells, including certain tumor cells, rely on for energy and building blocks. By blocking glutaminase, telaglenastat aims to disrupt this metabolic pathway, affecting the growth and survival of these cells.
Many tumors show an increased dependency on glutamine for their rapid growth. Glutaminase converts glutamine into glutamate, which fuels energy production and the synthesis of various cellular components like amino acids, fatty acids, and nucleotides. By inhibiting glutaminase, telaglenastat is designed to deplete glutamine and its downstream metabolites, potentially starving these dependent cells of the nutrients they need to grow and proliferate.
Its Role in Clinical Trials
Telaglenastat is being investigated for its potential in treating various types of cancer, particularly those that exhibit a high dependence on glutamine metabolism. These include solid tumors such as renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and triple-negative breast cancer (TNBC). It is also being explored in hematologic malignancies like multiple myeloma and myelodysplastic syndromes (MDS).
The drug has progressed through different phases of clinical trials to assess its safety and efficacy. In Phase 1 studies, telaglenastat was evaluated in patients with advanced or metastatic solid tumors to determine a safe dose and observe preliminary activity. The recommended Phase 2 dose was identified as 800 mg taken twice daily.
Further investigations have included Phase 2 trials, often combining telaglenastat with other anti-cancer therapies. For instance, in patients with advanced renal cell carcinoma, telaglenastat has been studied in combination with everolimus or cabozantinib. The ENTRATA study, a Phase 2 trial, explored telaglenastat plus everolimus in heavily pre-treated patients with metastatic RCC, showing an improvement in progression-free survival compared to placebo plus everolimus. However, another Phase 2 trial, CANTATA, evaluating telaglenastat with cabozantinib in metastatic clear cell RCC, did not show an improvement in progression-free survival.
Telaglenastat is also being studied in patients with specific genetic mutations, such as NF1, KEAP1/NRF2, or STK11/LKB1 aberrations in solid tumors or malignant peripheral nerve sheath tumors. These ongoing trials aim to understand how well telaglenastat works in these specific patient populations and to identify potential response mechanisms.
Potential Adverse Effects
Telaglenastat has shown a range of potential adverse effects in patients participating in clinical trials. Common side effects observed include fatigue and nausea, reported in 23% and 19% of patients, respectively, in a Phase 1 study. Other observed effects include decreased appetite, diarrhea, anemia, and elevated transaminases.
While generally considered well tolerated, some patients experienced more significant adverse events. For example, a grade 3 pruritic rash and thrombocytopenia have been reported as dose-limiting toxicities in some trials.
The full spectrum of side effects may still be emerging as more data from ongoing clinical trials become available. The safety profile of telaglenastat, especially when combined with other therapies, continues to be monitored closely during its development.