Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Harding JJ

PROVIDER: S-EPMC9401498 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Harding James J JJ Telli Melinda M Munster Pamela P Voss Martin H MH Infante Jeffrey R JR DeMichele Angela A Dunphy Mark M Le Mai H MH Molineaux Chris C Orford Keith K Parlati Frank F Whiting Sam H SH Bennett Mark K MK Tannir Nizar M NM Meric-Bernstam Funda F

Clinical cancer research : an official journal of the American Association for Cancer Research 20210720 18

<h4>Purpose</h4>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.<h4>Patients and methods</h4>Dose escalation by 3 + 3 design was fol ...[more]

PMID: 34285061

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Dataset Information

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

Purpose

Patients and methods

Results

Conclusions

Publications

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

Similar Datasets

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