3102 Background: MK4827 is an orally active, PARP 1/2 inhibitor with nanomolar potency. It induces selective synthetic lethality in homologous recombination (HR) repair deficient tumors with BRCA1/2 loss and in tumor cell lines with non-BRCA-related HR defects, supporting broad clinical application. A phase I study was undertaken to determine the toxicity and tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles, and preliminary anti-tumor activity. Methods: Patients (p) with advanced solid tumors enriched for BRCA-mutation carriers (BRCA-MC) and non-BRCA HR defects received once daily, escalating doses of MK4827 in cohorts of 3-6 p. Dose escalation was guided by toxicity, PK and PD data. Results: 60 p (M13, F47; median age 56 yr; 21 BRCA-MC) were treated at 10 dose levels from 30mg to 400mg on days 1-21 of a 28 day cycle (C) in C1, followed by continuous dosing. 20 additional p with soc were enrolled at the MTD. Prior systemic treatments were ≤2 (23p), ≥3 (17p), and ≥4 (40p). Overall, DLT ...