Abstract OT3-04-02: The DORA trial: A non-comparator randomised phase II multi-center maintenance study of olaparib alone or olaparib in combination with durvalumab in platinum treated advanced triple negative breast cancer (TNBC)
Authors: Dent R , Tan T , Kim S-B , Traina T , McArthur H , Im Y-H , Creel T , Blackwell K 
Published: February 2018

Abstract
Background: Recent data from the OlympiaD study revealed an improvement in response rate and progression-free survival (PFS) with the PARP inhibitor (PARPi) olaparib vs. standard of care chemotherapy in patients with metastatic breast cancer who harbor germline BRCA (gBRCA) mutations. Maintenance PARPi has improved median PFS in relapsed ovarian cancer regardless of gBRCA mutation status or HRD status. The similarities between the molecular aberration profiles of high-grade serous ovarian cancer and TNBC invites exploration of maintenance PARPi in mTNBC. Furthermore, because durable responses have been reported in subsets of patients with metastatic TNBC (mTNBC) with checkpoint blockade and because high mutational load is associated with both gBRCA and TNBC, these patients may be particularly susceptible to immunotherapy with PARPi. Thus, we hypothesize that olaparib either alone or in combination with the PD-L1 inhibitor durvalumab will be active in TNBC subjects who have responded to platinum-based chemotherapy.
Trial design: DORA is a non-comparator randomized, international, multicenter phase II study designed to explore the efficacy of olaparib with or without durvalumab as maintenance therapy in platinum-treated mTNBC. Subjects will be enrolled following four cycles of treatment with a platinum-based (cisplatin or carboplatin) chemotherapy as single agent or combination therapy. Subjects deriving clinical benefit (CR / PR / SD) with platinum-based therapy as determined by the treating physician will be eligible and randomized in a 1:1 ratio. Patients in arm 1 will receive olaparib orally 300mg BID continuously and in arm 2 will receive olaparib orally 300mg BID continuously in combination with durvalumab 1500mg IV every 4 wks. Tumor responses will be assessed every 8 wks.
Eligibility criteria: Subjects with mTNBC who are receiving platinum-based chemotherapy and who have had no more than 2 lines of chemotherapy in the metastatic or advanced setting, with one of those being a platinum, will be included in this trial. Eligible patients must have been assessed by their treating physicians to have derived clinical benefit with platinum based therapy. Archival tissue or fresh biopsy samples are mandated for biomarker analyses.
Aims:The primary endpoint is PFS; the key secondary endpoint is overall survival.
Statistical methods: The sample size is calculated based upon data derived from contemporary trials of chemotherapy in mTNBC. In both arms of the study, it is proposed to test a null hypothesis of a median PFS of 2 months against an alternative hypothesis of a median PFS of 4 months; there is no intention to make a formal statistical comparison between the two treatment arms. To test this hypothesis, assuming an exponential PFS distribution, use of an exponential MLE test, a two-sided significance level of 5% and a power of 90%, 25 subjects are required per arm.
Target accrual: To allow for a drop-out rate of approximately 20%, the sample size per arm will be inflated to 30 subjects. We plan to enroll approximately 60 subjects with mTNBC from 6 centers.
ClinicalTrials.gov Identifier: NCT03167619
Citation Format: Dent R, Tan T, Kim S-B, Traina T, McArthur H, Im Y-H, Creel T, Blackwell K. The DORA trial: A non-comparator randomised phase II multi-center maintenance study of olaparib alone or olaparib in combination with durvalumab in platinum treated advanced triple negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT3-04-02.