Phase I trial of the PARP inhibitor veliparib (V) in combination with carboplatin (C) in metastatic breast cancer (MBC).

1074 Background: Poly(ADP-ribose) polymerase (PARPi) inhibitors have shown activity in BRCA mutant and triple negative breast cancers (TNBC). The ideal dose and schedule of C and oral PARPi V is not known. We used sequential fluoro-3’-deoxythymidine (FLT) PET imaging and correlated tumor uptake to C with varying doses/schedules of V. Methods: To identify the recommended phase 2 dose (RP2D) of V when combined with C in patients (pts) with MBC with either TNBC or HER2 negative/estrogen receptor positive tumors with defective Fanconi Anemia (FA) pathway (i.e. no FANCD2 foci in nuclei of proliferating tumor cells via FA Triple Stain Immunofluroscence test), we used a standard 3+3 phase I design. Escalating doses of V were evaluated on a 7, 14, or 21-day schedules (table). Response was based on RECIST criteria using FDG PET/CT scans. FLT PET was done at baseline, cycle 1 day 7 and 14 or 21 and after cycle 3. Lesions were track-matched with FDG PET/CT and semi-quantitatively assessed using 2D ROI placement in a...