A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of AG-120 in Combination with Azacitidine in Subjects ≥ 18 Years of Age with Previously Untreated Acute Myeloid Leukemia with an IDH1 Mutation
Study AG120-C-009 is a global, Phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy and safety of AG-120 + azacitidine vs placebo + azacitidine in adult subjects with previously untreated IDH1m AML who are considered appropriate candidates for non-intensive therapy. The primary endpoint of OS is defined as the time from date of randomization to the date of death due to any cause. The key secondary efficacy endpoints are EFS, CR rate, CR + CRh rate (with CRh derived by Sponsor), and ORR. Following provision of signed informed consent, all subjects will undergo Screening procedures within 4 weeks (28 days) prior to randomization to determine eligibility. Gene mutation analysis for confirmation of IDH1m disease from a bone marrow and/or peripheral blood sample and germ-line mutation analysis from a buccal swab will be conducted for all subjects, and can be conducted prior to the 28-day Screening window. Central laboratory confirmation of IDH1m status is required for study entry. Additional Screening procedures include, but are not limited to: medical and medication history; bone marrow aspirate/biopsy for morphologic analyses and cytogenetics; complete physical examination; vital signs; 12-lead electrocardiogram (ECG); Eastern Cooperative Oncology Group (ECOG) performance status; echocardiogram (ECHO) or multi-gated acquisition (MUGA; not permitted for subjects in Germany) scan for left ventricular ejection fraction (LVEF); clinical laboratory assessments (hematology, chemistry, coagulation, and serum pregnancy test); QoL assessments; and exploratory biomarker assessments. Subjects eligible for study treatment based on Screening assessments will be randomized 1:1 to receive oral AG-120 or matched placebo, both administered in combination with subcutaneous (SC) or intravenous (IV) azacitidine. Randomization will be stratified by de novo status (de novo AML and secondary AML) and geographic region (United States/Canada; Western Europe, Israel, and Australia; and rest of world [ROW]). Subjects should be treated for a minimum of 6 cycles of combination therapy unless they experience relapse after achieving a CR, CRi (including CRp), or MLFS; disease progression after having previously attained PR or stable disease; unacceptable toxicity (adverse event [AE]); confirmed pregnancy; withdrawal by subject; physician’s decision to end treatment; protocol violation; death; or End of Study.
• All subjects will receive azacitidine 75 mg/m2/day SC or IV for the first 1 week (7 days) (or on a 5-2-2 schedule) of each 4-week (28-day) cycle in combination with AG-120 or placebo once daily (QD) on each day of the 4-week cycle. The same schedule should be used for each subject throughout the duration of treatment, when possible. • Subjects should continue to receive therapy with AG-120 or placebo + azacitidine until death, disease relapse, disease progression, development of unacceptable toxicity (AE), confirmed pregnancy, withdrawal by subject, physician’s decision to end treatment, protocol violation, or End of Study.
