Safety, pharmacokinetics (PK), and pharmacodynamics (PD) of HGS1029, an inhibitor of apoptosis protein (IAP) inhibitor, in patients (Pts) with advanced solid tumors: Results of a phase I study.

Abstract

3008 Background: IAPs are key regulators of cancer cell survival, which makes them appealing targets for cancer therapy. HGS1029 is a small molecule IAP inhibitor which directly kills tumor cells as a single-agent or in combination. Methods: The safety, PK and PD (various cytokines and apoptotic markers) of HGS1029, given as a 15 min IV infusion with Schedule (Sch) A (Day 1, 8 and 15 every 28D) and then Sch B (continuous weekly) were evaluated in pts with advanced solid tumors. Results: 44 pts (20 females, 24 males) with a median age of 62 years (range: 41-88) have been enrolled in 10 cohorts (Sch A: 0.1, 0.2, 0.4, 0.6, 0.9, 1.4, 2.1 and 3.2 mg/m2; Sch B: 3.2 and 4.8 mg/m2). Dose-limiting toxicities (DLTs) were observed in 1/9 pts at 1.4 mg/m2 (Grade (G) 3 AST, G3 amylase, G4 lipase, and G3 fatigue) and in 2/6 pts at 4.8 mg/m2 (G3 fatigue, prolonged asymptomatic G4 amylase and lipase). The most frequent adverse events (typically mild to moderate in severity), reported to be at least possibly related to HG...