ABT-199 (GDC-0199) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL): High complete- response rate and durable disease control.

7015 Background: Overexpression of Bcl-2 in relapsed CLL/SLL is associated with dysregulated apoptosis and chemoresistance. ABT-199 is an orally bioavailable, selective Bcl-2 inhibitor that triggers apoptosis of CLL cells in vitro and in vivo, making it a promising agent for the treatment of patients (pts) with CLL/SLL. Methods: The primary objectives of this phase I study were to evaluate the safety and pharmacokinetics (PK) and to determine the maximum tolerated dose and a recommended phase 2 dose (RPTD) of ABT-199. A secondary objective was to assess preliminary efficacy. Following early events of tumor lysis syndrome (TLS), a weekly ramp-up period to the final cohort dose (150 – 1200 mg) was implemented. Pts are now being enrolled in the safety expansion (SE) cohort. A ramp-up period with weekly dose increases occurred from 20, 50, 100, 200 mg to the final RPTD of 400 mg. Results: As of 12/04/2013, 84 pts (11 in SE) were enrolled with a median time on study of 14.7 (range, 0.5-29.3) months. 23 (27%) p...