2092 Background: Niraparib (Np) is an oral, highly potent and selective PARP1/2 inhibitor. The hypothesis for this study is 1) PARP inhibition of DNA repair damage is potentiated with TMZ. 2) PARP inhibition restores sensitivity to TMZ mismatch repair-deficient tumors. Methods: This was a multi-center (3), open-label, non-randomized two-part study in patients with advanced cancers. Patients were treated with Np (once daily continuously) + TMZ (once daily for first five days) in 28-day treatment cycles. In Part A, the objective was to determine the preliminary MTD of the two drugs in combination. Part B was to explore the efficacy and tolerability of this combination in two cohorts (recurrent GBM and melanoma). The study was closed after defining MTD in Part A. Results: There were 19 patients treated in Part A with Np at 3 dose levels 30 mg (6 subjects), 40 mg (10 subjects), and 70 mg (3 subjects) and 150 mg/m2 TMZ once daily. The MTD and RP2D was determined to be 40 mg Np and 150 mg/m2 TMZ. The DLT of Gra...