221TiP - A randomized phase II study to investigate the addition of PD-L1 antibody MEDI4673 (durvalumab) to a taxane-anthracycline containing chemotherapy i...

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Breast Cancer, Early Stage
Presenter Sibylle Loibl
Citation Annals of Oncology (2016) 27 (6): 43-67. 10.1093/annonc/mdw364
Authors S. Loibl1, A. Schneeweiss2, N. Burchardi3, J. Blohmer4, C. Hanusch5, S.D. Costa6, J. Huober7, C. Jackisch8, G. von Minckwitz9, S. Kümmel10, S. Paepke11, C. Denkart12, M. Untch13
  • 1Medicine And Research, German Breast Group, 63263 - Neu-Isenburg/DE
  • 2National Center For Tumor Diseases, University Hospital, Heidelberg/DE
  • 3Medicine And Research, German Breast Group (GBG) Forschungs GmbH, Neu-Isenburg/DE
  • 4Brustzentrum, Charite Berlin Mitte, Berlin/DE
  • 5Frauenklinik, Rotkreuzklinikum München, München/DE
  • 6Universitätsfrauenklinik Magdeburg, Otto-von Guericke-Universität, Magdeburg/DE
  • 7Gynecology, Ulm Medical University, Ulm/DE
  • 8Frauenklinik, Sana Klinikum Offenbach, Offenbach/DE
  • 9Department Of Medical Oncology, German Breast Group, Neu-Isenburg/DE
  • 10Frauenklinik, Kliniken Essen Mitte Evang. Huyssens-Stiftung, Essen/DE
  • 11Frauenklinik, Technische Universität München, München/DE
  • 12Institute Of Pathology, Charite Berlin Mitte, Berlin/DE
  • 13Frauenklinik, Helios Klinikum Berlin Buch, Berlin/DE

Abstract

Background

Chemotherapy (CT) is the only treatment option in triple negative breast cancer (TNBC) since so far no targeted agents are available. High amounts of tumor infiltrating lymphocytes (TILs) in TNBC are associated with higher treatment response and better outcome. Immunotherapy alone or in combination might be used to increase pathological complete response (pCR, ypT0 ypN0). Adding an anti-PD-L1 checkpoint inhibitor (Durvalumab) to standard CT might be a valid option.

Trial design

GeparNuevo will randomize patients to Durvalumab 1500 mg i.v. or placebo every 4 weeks. Monotherapy (750 mg i.v.) is given for the first 2 weeks (window phase), followed by a biopsy and Durvalumab/placebo plus nab-paclitaxel (nP) 125 mg/m2 weekly for 12 weeks followed by Durvalumab/placebo plus epirubicin/cyclophosphamide every 2 weeks for 4 cycles. Randomization will be stratified by TILs. Patients with primary cT1b-cT4a-d disease, centrally confirmed TNBC, and Ki-67 and TILs status on core biopsy can be included. Stromal TILs will be evaluated as no (≤10%) vs intermediate (11-59%) immune infiltrate vs lymphocyte predominant breast cancer (≥60%). PD-L1 status, immune markers and other predefined biomarkers will be prospectively assessed. Primary objective is to compare pCR rates. Secondary objectives are pCR rates in stratified subpopulations and according to other definitions; response rates; breast conservation rate; toxicity and compliance; quality of life; and survival. Change in TILs, Ki67 and other biomarkers before CT, after the window phase and after CT will be correlated with outcome. Six safety interim analyses focusing especially on immune-mediated adverse events are planned. It is planned to recruit 174 patients into this phase II trial. Recruitment has started in QII/2016 and is planned for 18 months in 30 sites in Germany.

Legal entity responsible for the study

German Breast Group

Funding

AstraZeneca

Disclosure

All authors have declared no conflicts of interest.