Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

281TiP - A phase Ib/II study of Durvalumab combined with dose-dense EC in neoadjuvant setting for patients with locally advanced luminal B HER2(-) or triple negative breast cancers (B-IMMUNE).

Presentation Number
281TiP
Lecture Time
12:45 - 12:45
Speakers
  • Alix Devaux (Brussels, BE)
Location
Hall A3 - Poster Area Networking Hub, ICM M√ľnchen, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Most patients with advanced breast cancer (BC) do not respond to immunotherapy with immunostimulating antibodies. Breast tumours are considered poorly antigenic due to a low mutational load, yet they contain tumour-infiltrating lymphocytes (TILs). As continuous immune pressure selects tumours that escape immune destruction, there is growing interest for the use of immunostimulatory antibodies for early-stage cancers. Based on data suggesting that anthracyclines increase tumour immunogenicity, we initiated a phase Ib/II trial to study the safety and efficacy of the anti-PD-L1 antibody durvalumab combined to epirubicin in the neoadjuvant setting for localized BC.

Trial design

B-IMMUNE study is a multicentric prospective trial including luminal B HER2(-) and triple negative BC (TNBC) patients. The study includes two parts. First a phase Ib with a 3 + 3 design whose primary objective is to evaluate the safety of an increasing number of durvalumab infusions associated to dose-dense Epirubicin-Cyclophosphamide (EC) after weekly paclitaxel for 12 weeks in the neoadjuvant setting. Then, if the durvalumab-EC combination is safe, a phase II will be initiated with an open-label 4:1 randomization in favour of the experimental durvalumab arm. Its primary objective is to evaluate clinical efficacy based on the complete pathological response rate (pCR) compared to historical controls (15% for luminal B HER2(-) BC and 30% for TNBC). The phase II will include 24 luminal B HER2(-) BC patients and 22 TNBC patients, allowing to detect pCR rate improvements of 40% and 60%, respectively (α ≤ 0.1 and β ≤ 0.1). Exploratory objectives include the identification of predictive biomarkers for anti-PD-L1 efficacy with a focus on the TCR repertoires of tumour-infiltrating T cells collected before and after durvalumab. Translational research will evaluate the presence of tumour-specific CD8 T cells among TILs and the influence of durvalumab on this population using the control arm as a reference.

Clinical trial identification

NTC03356860, ONCOGHdC2015_01, November 29, 2017.

Legal entity responsible for the study

Grand Hôpital de Charleroi (GHdC).

Funding

AstraZeneca, Télévie (FNRS).

Disclosure

J. Carrasco: Research grant: AstraZeneca. All other authors have declared no conflicts of interest.

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