On October 21, 2014 Agios Pharmaceuticals reported the initiation of a Phase 1/2 multicenter study of AG-221 in patients with advanced solid tumors, including gliomas, as well as angioimmunoblastic T-cell lymphoma (AITL) that carry an isocitrate dehydrogenase-2 (IDH2) mutation (Press release Agios Pharmaceuticals, OCT 21, 2014, View Source [SID:1234500851]). The study will enroll patients who have recurred or progressed following standard therapy or have not responded to prior standard therapy. This is the second trial to be initiated in patients with cancer as part of AG-221’s clinical development program, which includes the ongoing Phase 1 trial with four expansion cohorts in patients with hematologic malignancies.

Preclinical evidence shows that mutant IDH2 enzyme, the target of AG-221, produces 2-hydroxyglutarate (2HG), which blocks the normal maturation of progenitor cells. In solid tumor 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 tumors. In addition, AG-221 has demonstrated 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.

“Evaluating AG-221 in patients with advanced solid tumors 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,” said Chris Bowden M.D., chief medical officer at Agios. “The safety, pharmacokinetics, clinical activity, and effect on the biomarker 2HG we have observed from the different dose levels studied in the Phase 1 trial for advanced hematologic malignancies give us insights into the potential to fight cancer in patients with advanced solid tumors. 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.”