Background: To establish the maximum-tolerated dose (MTD) and evaluate dose-limiting toxicities (DLTs) and response to therapy of combination therapy with carboplatin/paclitaxel and olaparib, an oral tablet inhibitor of poly ADP ribose polymerase (PARP) of BRCA 1 and 2, in advanced (Stage III or IV) relapsed ovarian cancer. Methods: Eligibility required measurable disease, adequate organ function and ECOG performance status of ≤ 2. Subjects had to have failed first line platinum containing chemotherapy. All subjects were tested for BRCA 1 and 2. Subjects received the metronomic therapy of paclitaxel 60mg/m2 IV and carboplatin AUC 2 IV weekly, 3 weeks out of 4 and increasing doses of olaparib until the maximum tolerated dose was obtained. Olaparib started at 50 mg bid administered orally for 3 consecutive days (D1-D3), every week for each cycle. Subjects were assessed for toxicity and response according to the protocol. Subjects received combination therapy until DLT or disease progression. Results: The MTD was found to be olaparib 150 mg bid, three (D1-D3) consecutive days of each week of each cycle. Total number of patients enrolled in the phase 1b part of this study was 14. Median age was 58. Median number of prior therapeutic regimens was 4. Median number of cycles on study to date is 9.3. There have been no deaths due to study regimen or grade 4 toxicities. The most common grade 3 toxicities were neutropenia, lymphopenia, anemia, fatigue, and MDS (1pt.). There was no evidence of GI, cardiac, hepatic, pulmonary or dermatologic toxicities in any of these patients. 4 subjects had a complete remission (CR), 3 had partial remissions (PR), 3 had stable disease (SD), 2 had progressive disease (PD) and 2 were not evaluable. Of the 4 CR’s three were BRCA positive Of the PR’s two were BRCA positive and one was variant. Of the SD’s there were 2 BRCA positive. Of the PD’s one was BRCA positive. Conclusions: Olaparib, an oral tablet can be safely administered with a weekly regimen of carboplatin and paclitaxel in heavily pretreated, ovarian cancer patients. This is the first successful combination of olaparib with carboplatin and paclitaxel that has been well tolerated with minimal toxicity. Clinical trial information: NCT01650376.