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% tumor

SUBMITTER: Harding JJ 

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

REPOSITORIES: biostudies-literature