A phase I dose-escalation and expansion study of telaglenastat in patients with advanced or metastatic solid tumors Journal Article
| Authors: | 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. |
| Article Title: | 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 þ 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. 2021 The Authors; Published by the American Association for Cancer Research |
| Journal Title: | Clinical Cancer Research |
| Volume: | 27 |
| Issue: | 18 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2021-09-15 |
| Start Page: | 4994 |
| End Page: | 5003 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-21-1204 |
| PUBMED: | 34285061 |
| PROVIDER: | scopus |
| PMCID: | PMC9401498 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2021 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work