Abstract CT221: Mutanome engineered RNA immuno-therapy (MERIT) for patients with triple negative breast cancer (TNBC)
Authors: Heesen Ludwig , Frenzel Katrin , Bolte Stefanie , Bukur Valesca , Diken Mustafa , Derhovanessian Evelyna , Kreiter Sebastian , Kuhn Andreas N. , Kühlcke Klaus , Löwer Martin , Lindman Henrik , Pascolo Steve , Schmidt Marcus , Schneeweiss Andreas , Sjöblom Tobias , Thielemans Kris , Zitvogel Laurence , Türeci Özlem , Sahin Ugur 
Published: August 2019

Abstract
Background: Treatment of triple negative breast cancer (TNBC) is hampered by lack of established therapeutic targets like hormone receptors or HER-2. Surgery, chemotherapy and radiotherapy are the standard of care yet cure rates in patients with TNBC remain inferior compared to other BC subtypes. Approaches tailored to the patient’s individual tumor signature may lead to improvement. The “Mutanome Engineered RNA Immuno-Therapy (MERIT)” consortium is validating an innovative individualized mRNA-based vaccine for TNBC treatment. MERIT is a collaboration of five European partners (academia and industry) dedicated to realizing a personalized approach for TNBC treatment. The consortium set up a clinical research program covering drug development from target discovery and validation to GMP manufacturing and drug release for each individual patient (MUTANOME). Moreover, the consortium also established a pre-synthesized mRNA vaccine warehouse containing the most frequently shared tumor-associated antigens (TAA) in TNBC for drug supply (WAREHOUSE).
Methods: A Phase I trial (NCT02316457) in two European countries is assessing the feasibility, safety and vaccine-induced immune response of this personalized immunotherapy. TNBC patients (pT1cN0M0 - TxNxM0) after surgery and (neo-)adjuvant chemotherapy are allocated to one of three study arms. Patients in ARM1 receive eight WAREHOUSE vaccinations with personalized TAA combinations corresponding to the patient’s tumor antigen-expression profile. Patients in ARM2 are first treated with the WAREHOUSE vaccine (optional) followed by eight vaccination cycles of an on-demand manufactured MUTANOME vaccine encoding the unique mutation signature of the individual patient identified by next-generation sequencing. Patients in ARM3 receive eight WAREHOUSE vaccinations including an additional helper RNA. The treatment of twelve patients in ARM1 is completed, while treatment of patients for ARM2 and ARM3 is ongoing. The mRNAs are administered intravenously as a RNA-lipoplex formulation, which BioNTech has previously shown is capable of protecting RNA from degradation, activating innate immunity, and transfecting APCs. Four clinical sites are open for recruitment; &gt;30 patients have been screened and vaccination with WAREHOUSE or MUTANOME RNA has started. Biomarker analysis is ongoing while the trial is continuing as planned. Preliminary data on the assessment of feasibility of WAREHOUSE and MUTANOME approaches will be given. We will give insights into features of the established process and upcoming adaptations in study design.
Citation Format: Ludwig Heesen, Katrin Frenzel, Stefanie Bolte, Valesca Bukur, Mustafa Diken, Evelyna Derhovanessian, Sebastian Kreiter, Andreas N. Kuhn, Klaus Kühlcke, Martin Löwer, Henrik Lindman, Steve Pascolo, Marcus Schmidt, Andreas Schneeweiss, Tobias Sjöblom, Kris Thielemans, Laurence Zitvogel, Özlem Türeci, Ugur Sahin. Mutanome engineered RNA immuno-therapy (MERIT) for patients with triple negative breast cancer (TNBC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT221.