Telaglenastat
Telaglenastat (CB-839), oral glutaminase 1 inhibitor
Written by Aaron CuhaReviewed Sep 2026
Also known as: CB-839, Telaglenastat hydrochloride
The only glutaminase inhibitor with randomised human data, and the data are oncology. Its pivotal trial in 444 patients with kidney cancer found median progression-free survival of 9.2 months against 9.3 on placebo. It has never been tested for senescence in a person.
Overview
Telaglenastat is an orally bioavailable, selective inhibitor of glutaminase 1, the enzyme that converts glutamine to glutamate. It matters to this catalogue because glutaminase inhibition is a senolytic mechanism in mice: senescent cells depend on glutaminolysis to buffer the acidity caused by lysosomal damage, and blocking it kills them. Telaglenastat is the clinical-stage compound in that class, which is why it appears on lists of senolytics. Every human trial of it is an oncology trial.
The pivotal trial, CANTATA, randomised 444 patients with metastatic clear-cell renal cell carcinoma to cabozantinib with telaglenastat or with placebo, double blind, at sites in the United States, Europe, Australia and New Zealand. Median progression-free survival was 9.2 months with telaglenastat and 9.3 months with placebo, hazard ratio 0.94, 95 percent confidence interval 0.74 to 1.21, P = 0.65. Response rates were 31 percent versus 28 percent. Grade 3 to 4 adverse events occurred in 71 percent and 79 percent of patients. The trial was manufacturer funded and the authors concluded telaglenastat did not improve the efficacy of cabozantinib.
The smaller ENTRATA trial randomised 69 heavily pretreated patients 2:1 to everolimus with telaglenastat or placebo, with progression-free survival tested at a one-sided alpha below 0.2, an unusually permissive threshold. Median progression-free survival was 3.8 months versus 1.9 months, hazard ratio 0.64, one-sided P = 0.079. Grade 3 to 4 events occurred in 74 percent versus 61 percent. The registry shows the pattern that followed: KEAPSAKE in lung cancer terminated after 40 patients, a talazoparib combination terminated, a nivolumab combination terminated, and several academic trials still active.
No trial of telaglenastat has measured senescence, frailty or any ageing endpoint. No senolytic has improved a clinical outcome in a randomised trial in humans, and the compound with the most human data in this mechanistic class was tested only against cancer.
Mechanism of action
Established in humans as pharmacology and in mice as senolysis, and these should not be merged. In people, telaglenastat blocks glutaminase 1, reducing the tumour's ability to use glutamine for biosynthesis; this was the rationale for combining it with cabozantinib and everolimus. In mice and in human cells, glutaminase inhibition kills senescent cells by removing the ammonia that neutralises their lowered internal pH. Nobody has shown telaglenastat clears senescent cells in a person.
Human evidence
Extensive, randomised, and entirely in cancer. Two randomised placebo-controlled trials plus phase 1 dosing work, in several hundred patients. No human trial has measured a senescence or ageing endpoint.
- CANTATA, 444 patients with metastatic renal cell carcinoma: no progression-free survival benefit (9.2 versus 9.3 months, hazard ratio 0.94, P = 0.65). Manufacturer funded, primary endpoint missed.
- ENTRATA, 69 patients: median progression-free survival 3.8 versus 1.9 months, hazard ratio 0.64, one-sided P = 0.079 against a pre-specified one-sided alpha below 0.2. A small trial tested at a permissive threshold, and its result did not survive into the larger trial.
- Grade 3 to 4 adverse events were common in both trials and in both arms, which is expected in this population and worth knowing before imagining the drug as a geroprotector.
- Registry status September 2026: KEAPSAKE terminated after 40 patients, a talazoparib combination terminated after 33, a nivolumab combination terminated after 118. Several investigator-led trials remain active, including one in pulmonary hypertension not yet recruiting.
What this does not tell you: These trials tell you what adding a glutaminase inhibitor to cancer therapy does to tumour progression in people with advanced cancer. They do not measure senescent cell burden, physical function, frailty or any ageing outcome, and the doses and durations were set for oncology. A negative cancer trial is not evidence against the senolytic hypothesis, and it is not evidence for it either.
Reading the research record
Telaglenastat is on this site because it is what the glutaminolysis senolytic mechanism looks like when someone actually gives it to people at scale. The result is a reminder of how the field works: the mechanism was validated in mice, the only clinical-stage molecule went into oncology because that is where the money and the endpoints are, the pivotal trial missed, and the company programme contracted. None of that was a test of the ageing hypothesis.
The ENTRATA trial deserves a note on its own. A 69-patient trial designed with a one-sided alpha below 0.2 reported a hazard ratio of 0.64 at P = 0.079 and was described as improving progression-free survival. The larger, conventionally powered CANTATA found nothing. That sequence, a small permissive trial followed by a null pivotal trial, is the pattern this site tries to make visible rather than quote selectively.
The evidence, charted
Fig. 1 · evidence composition
5of 6 citations (83%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 3 distinct years, 2021 to 2026, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Not approved
UK
Approved
AU
Approved
CA
Not approved
Approved in 2 of 4, prescription route in 0, not approved in 2. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Fig. 4 · dose response
No human dose response curve exists
We draw this figure where the data supports it. For this compound in humans it does not, so the panel stays empty rather than borrowing an animal curve and implying it transfers.
Key studies & citations
- Human2022
Efficacy and Safety of Telaglenastat Plus Cabozantinib vs Placebo Plus Cabozantinib in Patients With Advanced Renal Cell Carcinoma: The CANTATA Randomized Clinical Trial
444 patients randomised, double blind, placebo controlled. Median progression-free survival 9.2 versus 9.3 months, hazard ratio 0.94, 95 percent confidence interval 0.74 to 1.21, P = 0.65. Overall response 31 versus 28 percent. Grade 3 to 4 adverse events in 71 versus 79 percent. Manufacturer funded. The primary endpoint was missed.
JAMA Oncology - Human2022
Telaglenastat plus Everolimus in Advanced Renal Cell Carcinoma: A Randomized, Double-Blinded, Placebo-Controlled, Phase II ENTRATA Trial
69 patients randomised 2:1 after a median of three prior lines. Median progression-free survival 3.8 versus 1.9 months, hazard ratio 0.64, 95 percent confidence interval 0.34 to 1.20, one-sided P = 0.079 against a pre-specified one-sided alpha below 0.2. One partial response on telaglenastat. Grade 3 to 4 events 74 versus 61 percent. Manufacturer funded.
Clinical Cancer Research - Human2022
Telaglenastat Plus Cabozantinib or Everolimus for Advanced or Metastatic Renal Cell Carcinoma: An Open-Label Phase I Trial
Open-label phase 1 combination work that set the doses used in the randomised trials above. Human safety and dosing data, no controlled efficacy comparison.
Clinical Cancer Research - Human2026
CANTATA: CB-839 With Cabozantinib vs. Cabozantinib With Placebo in Patients With Advanced Renal Cell Carcinoma
Calithera Biosciences, phase 2, 444 participants, status COMPLETED, results first posted March 2023. Registry record for the pivotal trial.
ClinicalTrials.gov - Human2026
KEAPSAKE: Telaglenastat With Standard-of-Care Chemoimmunotherapy in Non-Small Cell Lung Cancer
Phase 2, 40 participants enrolled, status TERMINATED, verified live September 2026. One of several company-sponsored telaglenastat trials stopped after CANTATA.
ClinicalTrials.gov - Animal2021
Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders
Mouse and human cells. The senolytic rationale for this drug class: glutaminase 1 is required for senescent cell survival, and inhibiting it in aged mice eliminated senescent cells and improved age-associated organ dysfunction. This is why telaglenastat appears on senolytic lists. It is a mouse result.
Science
Frequently asked questions
Is telaglenastat a senolytic?
It inhibits glutaminase 1, which is a senolytic mechanism in mice and in cultured human cells. Whether telaglenastat clears senescent cells in a person has never been measured, in any trial.
What happened in the CANTATA trial?
It missed its primary endpoint. In 444 patients with metastatic kidney cancer, median progression-free survival was 9.2 months with telaglenastat plus cabozantinib and 9.3 months with placebo plus cabozantinib, hazard ratio 0.94, P = 0.65. The trial was manufacturer funded.
Was the smaller trial positive?
ENTRATA reported median progression-free survival of 3.8 versus 1.9 months, hazard ratio 0.64, at a one-sided P of 0.079 against a pre-specified one-sided alpha below 0.2, which is a permissive threshold. The larger CANTATA trial then found no difference.
Could telaglenastat be repurposed for ageing?
No such trial is registered. The mouse work behind the idea is strong, the human work is oncology only, and the adverse event profile in cancer trials, with grade 3 to 4 events in most patients in both arms, is a long way from what a preventive geroprotector would need to show.