Phase I/Ib Study Of The Parp Inhibitor (Parpi) Olaparib (O) With Carboplatin (C) In Heavily Pretreated High-Grade Serous Ovarian Cancer (Hgsoc) At Low Genetic Risk (Nct01445418).

5514 Background: O is a FDA-approved PARPi for advanced ovarian cancer with germline BRCA mutation (gBRCAm). O and C each have shown single agent activity in HGSOC. We hypothesize that addition of O to C to stress DNA repair machinery is tolerable and of clinical benefit in HGSOC pts without gBRCAm. Methods: 3x3 dose escalation examined O capsules (400 mg q12h, d 1-7) with C AUC 3, 4, or 5 on d1 or 2 every 21d over 3 dose levels. No more than 8 O + C cycles were given, followed by daily O maintenance. Safety was assessed every cycle. Response was assessed every 2 cycles. PBMCs were collected at baseline, d3, and post-cycle 1 for PAR incorporation. Tumor biopsies were performed in a 15 patient (pt) expansion cohort at maximum tolerated dose (MTD) pre-and post-cycle 1 for proteomics and apoptosis endpoints. Results: 30 women (median age 65 [49-71]) were treated over 3 dose levels of O + C AUC3 (3 pts), AUC4 (MTD, 21 pts), and AUC5 (6 pts). 24 pts had negative gBRCAm testing and 6 had BRCAPRO score u003c 10% wit...