A Phase I Dose-Escalation and Expansion Study of Telaglenastat in Patients with Advanced or Metastatic Solid Tumors

Clin Cancer Res. 2021 Sep 15;27(18):4994-5003. doi: 10.1158/1078-0432.CCR-21-1204. Epub 2021 Jul 20.


Purpose: Glutamine is a critical fuel for solid tumors. Interference with glutamine metabolism is deleterious to neoplasia in preclinical models. A phase I study of the oral, first-in-class, glutaminase (GLS) inhibitor telaglenastat was conducted in treatment-refractory solid tumor patients to define recommended phase II dose (RP2D) and evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity.

Patients and methods: 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% GLS inhibition in platelets at plasma exposures >300 nmol/L, >75% tumoral GLS inhibition, and significant increase in circulating glutamine. RP2D was defined at 800 mg twice-daily. Disease control rate (DCR) was 43% across expansion cohorts (overall response rate 5%, DCR 50% in renal cell carcinoma).

Conclusions: Telaglenastat is safe, with a favorable PK/PD profile and signal of antitumor activity, supporting further clinical development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Comment

MeSH terms

  • Carcinoma, Renal Cell*
  • Enzyme Inhibitors
  • Humans
  • Kidney Neoplasms*
  • Maximum Tolerated Dose
  • Nausea
  • Neoplasms* / drug therapy


  • Enzyme Inhibitors