Abstract AP30: PHASE IB/II WITH EXPANSION OF PATIENTS AT THE MTD STUDY OF OLAPARIB PLUS WEEKLY (METRONOMIC) CARBOPLATIN AND PACLITAXEL IN RELAPSED OVARIAN CANCER PATIENTS

BACKGROUND: We established the olaparib tablet maximum tolerated dose (MTD) at 150 mg bid, dose limiting toxicities (DLT9s) and response to therapy or carboplatin, paclitaxel and olaparib tablet given simultaneously, reported at ASCO 2014. This abstract will include data from both the phase 1b and the phase 2 expansion. METHODS: A total of 54 subjects were evaluated in this trial, 14 in phase 1b and 40 in phase 2. Eligibility required measurable disease, adequate organ function and ECOG performance status of ~ 2. Subjects had to have failed first line platinum containing chemotherapy. BRCA testing was conducted as available. Subjects received the metronomic therapy of paclitaxel 60mg/m2 IV and carboplatin AUC 2 IV weekly, 3 weeks out of 4, and olaparib tablets at 150 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 that reached a confirmed complete remission were transitioned to olaparib tablets only, 300 mg bid until disease progression. RESULTS: Median age was 58 and median number of prior regimens was 4. There have been no deaths due to the study regimen. One patient had grade 4 neutropenia and an allergic reaction to carboplatin. The common grade 3/4 toxicities were caused by the chemotherapy (neutropenia. anemia and thrombocytopenia). Two patients had mild GI toxicities. One patient had a skin rash. There was no evidence of cardiac, hepatic, or pulmonary toxicities in any of these patients. 25% of subjects had a complete remission (CR), 31% had PR, 23% had SD and 21% had PD. Of the 13 CRs, 4 were BRCA negative. PFS median for BRCA positive subjects is 12.6 months vs 4.8 months for BRCA negative subjects. OS median for BRCA positive subjects is 24 months vs 16 months for BRCA negative subjects. All of the CR9s are alive. CONCLUSION: Olaparib tablet can be safely administered simultaneously with a weekly regimen of carboplatin and paclitaxel in heavily pretreated ovarian cancer patients. Olaparib appears to be highly effective in BRCA positive subjects. This is the first successful combination of olaparib tablets with carboplatin and paclitaxel that has been well tolerated. Citation Format: Rivkin SE, Moon J, Iriarte D, Sloan H, Wiseman C, Klee M, Ference K, Drescher C, Veljovich D, Bondurant A, Peters W, Jiang P, Goodman G, Park M, Fer M, Shah C, Johnston E, Kaplan H, Wahl T, Ellis E. PHASE IB/II WITH EXPANSION OF PATIENTS AT THE MTD STUDY OF OLAPARIB PLUS WEEKLY (METRONOMIC) CARBOPLATIN AND PACLITAXEL IN RELAPSED OVARIAN CANCER PATIENTS [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr AP30.