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news.US-based Agios Pharmaceuticals has dosed first patient in a Phase I trial of single agent AG-881, a small molecule, in patients with advanced solid tumors with an isocitrate dehydrogenas (IDH) mutation.
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In preclinical studies, AG-881 was shown to fully penetrate the blood-brain barrier and inhibit IDH1 and IDH2 mutations in cancer models.
IDH1 and IDH2 are two metabolic enzymes that are mutated in a range of hematologic and solid tumor malignancies including acute myeloid leukemia (AML) and gliomas.
The multi-center, open-label, dose-escalation and expansion Phase I trial is designed to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-881 in advanced solid tumors.
In the trial, AG-881 will be administered continuously as a single agent dosed orally in a 28-day cycle.
Agios chief medical officer Dr Chris Bowden said: "The initiation of this study represents a significant milestone for Agios, as it marks the third program from our portfolio of IDH inhibitors to enter the clinic in less than two years.
"We look forward to producing important early data to guide our future development plans and continuing to demonstrate Agios’ leadership in cancer metabolism and drug development for IDH inhibitors."
The first portion of the trial includes a dose-escalation phase in which cohorts of patients will receive ascending oral doses of AG-881 to determine the maximum tolerated dose (MTD) and/or the recommended Phase II dose based on safety and tolerability.
The trial’s second portion is a dose expansion phase where patients will receive AG-881 to further evaluate the safety, tolerability and clinical activity of the recommended Phase II dose.
The company said that a second dose-escalating and expansion Phase I trial in hematologic malignancies is on track to begin dosing in coming weeks.
This second trial is for patients with advanced IDH1 or IDH2 mutant-positive hematologic malignancies whose cancer has progressed on a prior IDH inhibitor therapy.
The pan-IDH mutant inhibitor, AG-881, has been developed as part of a collaboration between Agios and Celgene.
The two firms have also created two other investigational medicines the IDH2 mutant inhibitor, AG-221 and the IDH1 mutant inhibitor, AG-120.
Image: Agios’ single agent AG-881 has shown to fully penetrate the blood-brain barrier and inhibit IDH1 and IDH2 mutations in cancer models. Photo: courtesy of Michelle Meiklejohn/ freedigitalphotos.net.