A randomized phase II study to investigate the addition of PD-L1 antibody MEDI4673 (durvalumab) to a taxane-anthracycline containing chemotherapy in triple negative breast cancer (GeparNuevo)

Date

10 Oct 2016

Session

Poster display

Presenters

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

Author affiliations

  • 1 Medicine And Research, German Breast Group, 63263 - Neu-Isenburg/DE
  • 2 National Center For Tumor Diseases, University Hospital, Heidelberg/DE
  • 3 Medicine And Research, German Breast Group (GBG) Forschungs GmbH, Neu-Isenburg/DE
  • 4 Brustzentrum, Charite Berlin Mitte, Berlin/DE
  • 5 Frauenklinik, Rotkreuzklinikum München, München/DE
  • 6 Universitätsfrauenklinik Magdeburg, Otto-von Guericke-Universität, Magdeburg/DE
  • 7 Gynecology, Ulm Medical University, Ulm/DE
  • 8 Frauenklinik, Sana Klinikum Offenbach, Offenbach/DE
  • 9 Department Of Medical Oncology, German Breast Group, Neu-Isenburg/DE
  • 10 Frauenklinik, Kliniken Essen Mitte Evang. Huyssens-Stiftung, Essen/DE
  • 11 Frauenklinik, Technische Universität München, München/DE
  • 12 Institute Of Pathology, Charite Berlin Mitte, Berlin/DE
  • 13 Frauenklinik, Helios Klinikum Berlin Buch, Berlin/DE
More

Resources

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.

Resources from the same session

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings