Inhibition of Poly (ADP-Ribose) Polymerase (PARP) by ABT-888 in Patients With Advanced Malignancies: Results of a Phase 0 Trial. Shivaani Kummar, MD National Cancer Institute June 3, 2007. Poly (ADP-Ribose) Polymerase (PARP). Conducted under the FDA’s Exploratory IND Guidance.
Shivaani Kummar, MD
National Cancer Institute
June 3, 2007
Conducted under the FDA’s Exploratory IND Guidance
Example 3: Clinical Studies of Mechanism of Action (MOA) Related to Efficacy
0, 2, 4, 7, 24 hr
given dose level, OR
3 patients at each dose level
The objective of dose escalation was to investigate a PD end-point, i.e. inhibition of PARP activityand not to determine the MTD.
Dose escalation continued with the goal to achieve significant PARP inhibition in tumor samples in 3 out of 3 participants at 2 dose levels.
PAR Inhibition in PBMCs
NCI’s PHASE 0 TEAM
James H. Doroshow
Anthony J Murgo
Joseph E. Tomaszewski
Ralph E. Parchment
All the present and future patient participants of Phase 0 trials