A phase I safety and pharmacokinetic (PK) study of navitoclax (N) in combination with docetaxel (D) in patients (pts) with solid tumors.

2518 Background: N (ABT-263) is a first-in-class orally available Bcl-2 protein inhibitor that in vitro and in vivo potentiates D activity across a variety of solid tumor types. This phase I study was performed to determine the maximum tolerated dose (MTD) and to assess the safety and PK profile of N plus D. Methods: Pts with advanced solid tumors, adequate organ function and ECOG performance status ≤1 were eligible. N at 150 and 200 mg was given PO, QD days (d) 1-3 or d1-5 q21 followed by D 75 mg/ m2 IV on d 1 q21. To compare the PK of either agent alone, N was administered on days 3-5 or 3-7 only in course 2. PK samples were collected for N and D in cycles 1 and 2. Adverse events (AE) were graded by NCI CTCAE V3.0. Results: 15 pts (M/F: 8/7; median age 54 yrs (range 30-71) were treated at 3 dose levels of N: 150 mg and 200mg d1-5 and 200 mg d1-3. DLTs were febrile neutropenia and grade (gr) 4 thrombocytopenia at N 200 mg d1-5 and febrile neutropenia at 200 mg d 1-3. The MTD is set at 150 mg N d1-5 with ...