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.
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).
AstraZeneca, Télévie (FNRS).
J. Carrasco: Research grant: AstraZeneca. All other authors have declared no conflicts of interest.