The purpose of this Phase I, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-120 in advanced hematologic malignancies that harbor an IDH1 mutation. The first portion of the study is a dose escalation phase where cohorts of patients will receive ascending oral doses of AG-120 to determine maximum tolerated dose (MTD) and/or the recommended Phase II dose. The second portion of the study is a dose expansion phase where four cohorts of patients will receive AG-120 to further evaluate the safety, tolerability, and clinical activity of the recommended Phase II dose. Additionally, the study includes a substudy evaluating the safety and tolerability, clinical activity, pharmacokinetics, and pharmacodynamics of AG-120 in subjects with relapsed or refractory myelodysplastic syndrome with an IDH1 mutation. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.
Subject must be ≥18 years of age.
Subjects must have documented IDH1 R132 gene-mutated advanced hematologic malignancy based on local or central evaluation.
Subjects must be amenable to serial bone marrow biopsies, peripheral blood sampling, and urine sampling during the study.
Subjects must have ECOG PS of 0 to 2.
Subjects who have undergone hematopoietic stem cell transplant (HSCT) within 60 days of the first dose of AG-120, or subjects on immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD). (The use of a stable dose of oral steroids post HSCT and/or topical for ongoing skin GVHD is permitted.)
Subjects who received systemic anticancer therapy or radiotherapy <14 days prior to their first day of study drug administration. (Hydroxyurea is allowed prior to enrollment and after the start of AG-120).
Subjects who received an investigational agent <14 days prior to their first day of study drug administration.
Subjects who are pregnant or breastfeeding.