Agios Pharmaceuticals has started a Phase I/II multicentre trial of AG-221 in patients with advanced solid tumours, including gliomas, as well as angioimmunoblastic T-cell lymphoma (AITL) that carry an isocitrate dehydrogenase-2 (IDH2) mutation.
The trial will enrol patients who have recurred or progressed following standard therapy or have not responded to prior standard therapy. It is designed to evaluate the clinical activity, safety and tolerability of AG-221.
The company said that this is the second trial to be started in patients with cancer as part of AG-221's clinical development programme, which includes the ongoing Phase I trial with four expansion groups in patients with haematologic malignancies.
Agios chief medical officer Dr Chris Bowden said: "Evaluating AG-221 in patients with advanced solid tumours is an important next step in our efforts to understand the potential of this investigational medicine to treat a broad range of cancers with the IDH2 mutation.
"The safety, pharmacokinetics, clinical activity, and effect on the biomarker 2HG we have observed from the different dose levels studied in the Phase I trial for advanced hematologic malignancies give us insights into the potential to fight cancer in patients with advanced solid tumours.
"AG-221 will only be evaluated in prospectively defined patients whose cancers carry an IDH2 mutation, and who we believe have the greatest potential to benefit from treatment."
In the multicentre, open-label, dose-escalation Phase I/II clinical trial, AG-221 will be given as a single agent and will be administered orally at an initial dose of 100mg once daily, in 28-day cycles.
The trial's key objectives include describing the dose-limiting toxicities and determining the maximum tolerated dose, evaluating the pharmacokinetic and pharmacodynamics, and characterising the clinical activity of AG-221.
Preclinical studies suggest that mutant IDH2 enzyme, the target of AG-221, produces 2-hydroxyglutarate (2HG), which blocks the normal maturation of progenitor cells.
In solid tumour cells expressing the IDH2 mutation, AG-221 inhibited the production of 2HG, which has the potential to affect differentiation and cell proliferation in patients with solid tumours.
Additionally, AG-221 has showed an acceptable safety profile and evidence of antitumor activity in the ongoing Phase I trial of AG-221 in patients with advanced hematologic malignancies that carry an IDH2 mutation.