Abstract OT3-01-01: BEGONIA: Phase Ib/II open-label, platform study of safety and efficacy of durvalumab, paclitaxel and other novel oncology therapy agents as first-line (1L) therapy in patients with metastatic triple negative breast cancer (mTNBC)

Background: Immuno-oncology therapies have shown durable clinical responses in a subset of patients with mTNBC. Combination therapy with checkpoint inhibition and chemotherapy is under investigation; preliminary research showed improved objective response rate (ORR) with combination therapy versus chemotherapy alone.1 Durvalumab is a selective, high-affinity, engineered, human monoclonal antibody that blocks programmed cell death-ligand 1 (PD-L1) binding to programmed cell death 1 (PD-1) and CD80 allowing T cells to recognize and kill tumor cells. This study is designed to assess the efficacy and safety of durvalumab + paclitaxel as 1L treatment in patients with mTNBC. Additionally, this study will also evaluate potential novel triplet treatment regimens of durvalumab + paclitaxel in combination with immune-modulating agents, selumetinib (ARRY-142886; AZD6244, an inhibitor of mitogen activated protein kinase/extracellular signal regulated kinase [MAPK/ERK]), danvatirsen (AZD9150, an antisense oligonucleotide designed to down-regulate expression of signal transducer and activator of transcription 3 protein), oleclumab (MEDI9447, an anti-CD73 monoclonal antibody), and capivasertib (AZD5363, a highly selective, oral, small molecule AKT inhibitor) that may provide further benefit to patients with mTNBC. Methods: BEGONIA is a phase Ib/II, open-label, multicenter, platform study (EudraCT No: 2018-000764-29) consisting of 2 parts: Part 1 is a phase Ib study planned to be conducted in approximately 100 patients (20 per arm) to assess the safety and tolerability of durvalumab (1500 mg intravenous [IV], q4w) + paclitaxel (90 mg/m2 IV, 4 week cycle, 3 weeks once weekly [days 1, 8, 15], 1 week off) (arm 1); and durvalumab + paclitaxel in combination with selumetinib (arm 2), danvatirsen (arm 3), oleclumab (arm 4) and capivasertib (arm 5) until disease progression. Dosing of the immune-modulating agents will be based on the previously defined recommended phase 2 doses of the component doublets (where available) in combination with durvalumab + paclitaxel using a rolling 6-patient design to evaluate for toxicity. Part 2 is a phase II study planned to be conducted in approximately 150 to 225 patients to evaluate efficacy of up to 2 best triplet combination arms based on their safety and efficacy outcomes in Part 1. The primary objective of Part 1 is safety and of Part 2 is efficacy (primary endpoint: progression free survival [PFS]); additionally, efficacy will be assessed in both parts, including overall survival, ORR, PFS, and duration of response (RECIST 1.1). Immunotherapy naive adult patients (≥18 years) with locally assessed and confirmed TNBC, ECOG PS 0 or 1, stage IV breast adenocarcinoma and no prior systemic treatment for metastatic disease will be enrolled. 1Adams et al., J Clin Oncol 2016;34(Suppl):abstr 1009 Citation Format: Schmid P, Nunes AT, Lall R, D9Cruz C, Grinsted L, Lanasa MC. BEGONIA: Phase Ib/II open-label, platform study of safety and efficacy of durvalumab, paclitaxel and other novel oncology therapy agents as first-line (1L) therapy in patients with metastatic triple negative breast cancer (mTNBC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT3-01-01.