Results presented at the 26th European Organisation for Research and Treatment of Cancer Symposium (18–21 November, Barcelona, Spain) by University of Colorado Cancer Center (CO, USA) investigator Daniel Pollyea show “extremely promising” early Phase I clinical trial results for the investigational drug AG-120 in a subset of patients with acute myeloid leukemia (AML) harboring mutations in the IDH1 gene.
These results add to promising Phase I results of AG-221, a related drug against mutations in IDH2, which were presented at the 2014 American Association for Cancer Research Annual Meeting (5–9 April, San Diego, CA, USA).
“This is one of the most exciting developments in AML in a long time,” Pollyea commented. He warns that the results are preliminary and based on just 17 patients, but states that: “Results have been dramatic.”
The IDH1 gene normally plays a role in Krebs cycle regulation; however, when mutated, a chain reaction is set off that results in failure of cells to mature, thus allowing for the development of AML. Mutations in IDH1 are found in 15–20% of all AML cases (~3500 cases of IDH1 AML every year). Preclinical studies demonstrated that AG-120 blocked the abnormal function of mutated IDH1 and restored natural development, resulting in the orderly death of leukemia cells. The US FDA recently granted Fast Track designation to the sister drug AG-221 (which, as mentioned, targets the IDH2 mutation), due to strong Phase I clinical trial results.
“This is a high-risk population and we hope that with continued successes we’ll be able to offer this therapy to more and more patients participating in this clinical trial,” Pollyea commented.
As explained by Pollyea, the University of Colorado clinical trial is predominantly for AML patients that have relapsed after prior treatments. “The test for the IDH mutation is done next door by the molecular lab at Children’s Hospital Colorado and we now offer the assay as a standard test for patients diagnosed with AML so that in the case of relapse we can quickly offer the clinical trial,” Pollyea remarked.
The AG-120 Phase I clinical trial for IDH1-mutant AML is also offered at Dana–Farber Cancer Institute (MA, USA) and Memorial Sloan Kettering Cancer Center (NY, USA), as well as a few other academic hospitals.