A Phase 1 Dose-Escalation and Expansion Study of Telaglenastat in Patients With Advanced or Metastatic Solid Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research Harding, J. J., Telli, M., Munster, P., Voss, M. H., Infante, J. R., DeMichele, A., Dunphy, M., Le, M. H., Molineaux, C., Orford, K., Parlati, F., Whiting, S. H., Bennett, M. K., Tannir, N. M., Meric-Bernstam, F. 2021


PURPOSE: Glutamine is a critical fuel for solid tumors. Interference with glutamine metabolism is deleterious to neoplasia in preclinical models. A Phase 1 study of the oral, first-in-class, glutaminase inhibitor telaglenastat was conducted in treatment-refractory solid tumor patients to define recommended phase 2 dose (RP2D) and evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity.EXPERIMENTAL DESIGN: Dose escalation by 3 +3 design was followed by exploratory tumor-/biomarker-specific cohorts.RESULTS: Among 120 patients, fatigue (23%) and nausea (19%) were the most common toxicity. Maximum tolerated dose was not reached. Correlative analysis indicated >90% glutaminase inhibition in platelets at plasma exposures >300 nM; >75% tumoral glutaminase inhibition; and significant increase in circulating glutamine. RP2D was defined at 800mg twice-daily. Disease control rate (DCR) was 43% across expansion cohorts (overall response rate 5%, DCR 50% in renal cell carcinoma).CONCLUSIONS: Telaglenastatis safe with a favorable PK/PD profile and signal of antitumor activity supporting further clinical development.

View details for DOI 10.1158/1078-0432.CCR-21-1204

View details for PubMedID 34285061