Introduction: The ability to use PBMCs as a surrogate for drug effect in tumor biopsies has obvious advantages. To assess whether there was a correlation between inhibition of PARP activity in PBMCs and tumor biopsies following administration of ABT-888, an inhibitor of PARP, we pooled data from 9 patients with advanced solid tumors enrolled on two different trials evaluating ABT-888. Methods: Paired PBMC and tumor biopsy samples were obtained before and after the first dose of ABT-888 in the phase 0 single-agent trial of ABT-888 (6 patients), and the phase 1 trial of ABT-888 in combination with topotecan (3 patients). The level of PARP activity was determined by measuring PAR by a validated ELISA. Results:$$table_{7394D07F-51A0-4453-9484-709493CC6BEB}$$ *3-6 hours post drug administration \#8224;3-6 hours post administration of the combination The overall correlation coefficient for the two measures of percent inhibition in PBMCs versus tumor is 0.90, suggesting that 81% of the variation from the mean for percent inhibition in tumor is predicted by percent inhibition in PBMCs. The 95% lower confidence bound on the correlation coefficient is 0.67. This indicates that there is 95% confidence that at least 45% of the variation from the mean for percent inhibition in tumor is predicted by percent inhibition in PBMCs. Conclusions: If these preliminary results are confirmed in a larger cohort of patients, the use of ABT-888 and possibly other PARP inhibitors in future trials might be guided by PAR measurements in PBMCs instead of tumor biopsies. Use of PBMCs as a tumor surrogate would allow repetitive, non-invasive monitoring of drug effect. The ability to relate PK exposure to PD response could provide important data for designing future clinical trials with these agents, and provide a model for other targeted agents. Funded in part by NCI Contract No. HHSN261200800001E.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5456.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO