99TiP - Mutanome Engineered RNA Immuno-Therapy (MERIT) for patients with Triple Negative Breast Cancer (99TiP)

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Drug Development
Bioethics, Legal, and Economic Issues
Presenter Katrin Frenzel
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors K. Frenzel1, L. Heesen1, S. Bolte1, V. Bukur1, M. Diken2, E. Derhovanessian1, S. Kreiter1, A. Kuhn1, K. Kuehlcke3, M. Löwer2, J. De Greve4, H. Lindman5, S. Pascolo6, M. Schmidt7, A. Schneeweiss8, T. Sjöblom9, K. Thielemans10, L. Zitvogel11, Ö. Türeci12, U. Sahin1
  • 1Biontech Group Mainz, BioNTech Group Mainz, 55131 - Mainz/DE
  • 2Tron Ggmbh, TRON, 55131 - Mainz/DE
  • 3Eufets Gmbh, EUFETS GmbH, Idar-Oberstein/DE
  • 4Department Medical And Molecular Oncology, UZ Brussels, Brussel/BE
  • 5Department Of Oncology, Uppsala University Hospital, Uppsala/SE
  • 6Urpp Translational Cancer Research, University of Zurich, Zurich/CH
  • 7Klinik Und Poliklinik Für Geburtshilfe Und Frauengesundheit, Universitätsmedizin Mainz, Mainz/DE
  • 8Sektion Gynäkologische Onkologie, NCT Heidelberg, Heidelberg/DE
  • 9Department Of Immunology, Uppsala University, Uppsala/SE
  • 10Dep. Immunology-physiology, University Hospital Brussel, Brussel/BE
  • 11Tumour Immunology And Immunotherapy, Gustave Roussy Institut de Cancérologie, 94805 - Villejuif/FR
  • 12Ci3 (cluster Of Individualized Immunointervention, CI3 (Cluster of Individualized Immunointervention, Mainz/DE

Abstract

Background

The treatment of triple negative breast cancer (TNBC) is hampered by the lack of established therapeutic targets like hormonal receptors or HER-2. Chemotherapy and radiotherapy is the standard of care and survival rates in TNBC remain poor. Approaches tailored to the patient’s individual tumor signature may bring improvement. The Mutanome Engineered RNA Immuno-Therapy (MERIT) consortium is validating an innovative, individualized mRNA-based vaccine for the treatment of TNBC. MERIT is a collaboration project of five European partners from academia and industry dedicated to realize a personalized approach for treatment of TNBC. The consortium has set up a clinical workflow, covering drug development from target discovery and validation to GMP manufacturing and drug release for each individual patient. Moreover, the consortium has generated a pre-synthesized mRNA vaccine warehouse containing the most frequent shared tumor antigens in TNBC for drug supply.

Trial design

A phase I trial in 4 European countries assesses the feasibility, safety and biological efficacy of this personalized immunotherapy. TNBC patients (pT1cN0M0 – TxNxM0) after surgery and adjuvant chemotherapy will be allocated to one of two study arms. Patients in ARM1 receive 8 vaccination cycles with a personalized set of shared tumor antigens from pre-synthesized mRNA vaccine warehouse that correspond to the patient tumor’s antigen-expression profile. Patients in ARM2 are first treated with the personalized WAREHOUSE vaccine approach followed by 8 vaccination cycles of an on-demand manufactured MUTANOME vaccine encoding unique mutation signature of the individual patient identified by NGS. The mRNAs are administered intravenously as a nanoparticulate lipoplex formulation, which protects RNA from degradation, activates innate immunity, transfects APCs and consequently induces highly potent antigen-specific T cell responses. Four clinical sites are open for recruitment; >10 patients have been screened and the vaccinations with pre-manufactured warehouse RNAs have started. We give insights into features of the established process and present first stratification data. MERIT is funded by the EU Commission’s FP7 and led by BioNTech AG.

Clinical trial identification

EudraCT No.: 2014-002274-37

Legal entity responsible for the study

BioNTech AG

Funding

European Commission’s FP7

Disclosure

K. Frenzel: Employee at BioNTech AG. L. Heesen, S. Bolte, V. Bukur, E. Derhovanessian: Employee of BioNTech AG. M. Diken: Employee of TRON gGmbH. S. Kreiter: BioNTech Group Mainz Advisor. A. Kuhn: Employee of BioNTech Group. K. Kuehlcke: Employee of BioNTech Group/Eufets. M. Löwer: Employee of TRON, Consultant for BioNTech Group. Ö. Türeci: Co-founder of Ganymed Pharmaceuticals AG. Inventor on 530 patents and patent applications. Member of Scientific Advisory Board of BioNTech AG. U. Sahin: Co-founder and CEO BioNTech AG, Mainz. Inventor of Licensed Patents related to Cancer Immunotherapy. Head of the Scientific Advisory Board of Ganymed Pharmaceuticals. T. Sjöblom: Founder, board member and shareholder of ExScale Biopecimen Solutions AB which markets CE/IVD solutions for nucleotide extraction in molecular pathology. K. Thielemans: eTheRNA Immunotherapies: receipt of grants, honoraria, consultation fees, Stock shareholder.

All other authors have declared no conflicts of interest.