A phase I trial of the human double minute 2 inhibitor (MK-8242) in patients with refractory/recurrent acute myelogenous leukemia (AML).

7070 Background: Human double minute 2 (HDM2) binds to and inhibits wild-type (WT) p53, thereby promoting oncogenesis. MK-8242 is a potent, orally bioavailable, small-molecule inhibitor of the HDM2:p53 protein-protein interaction being developed as a novel cancer therapy. Methods: This multi-center, non-randomized, open-label, 2-arm (A/monotherapy and B/combination therapy), 2-part (dose escalation and confirmation) study was designed to evaluate the safety/tolerability, pharmacokinetics (PK) and recommended phase 2 dose (RP2D) of MK-8242 +/- cytarabine in p53 WT patients (pts) with refractory/recurrent AML. The study was terminated for reasons unrelated to safety; only the monotherapy dose-escalation phase was completed. In Arm A, MK-8242 was initially dosed p.o. either QD (30 mg-250 mg) or BID (120 mg-250 mg) for 7 days on/7 days off (7on/7off) in a 28-day cycle The dosing schedule was later modified to 7on/14off in a 21-day cycle (210 mg or 300 mg BID) to improve the safety profile of the drug. Results...