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 5 European partners (academia and industry) dedicated to realize a personalized approach for TNBC treatment. The consortium set up a clinical workflow covering drug development from target discovery and validation to GMP manufacturing and drug release for each individual patient (MUTANOME). Moreover, the consortium established a pre-synthesized mRNA vaccine warehouse containing the most frequently shared tumor-associated antigens (TAA) in TNBC for drug supply (WAREHOUSE).
A phase I trial in 2 European countries assesses the feasibility, safety and biological efficacy of this personalized immunotherapy. TNBC patients (pT1cN0M0 – TxNxM0) after surgery and (neo-)adjuvant chemotherapy will be allocated to one of two study arms. Patients in ARM1 receive 8 WAREHOUSE vaccinations with personalized TAA combinations corresponding to the patient tumor’s antigen-expression profile. Patients in ARM2 are first treated with the WAREHOUSE approach followed by 8 vaccination cycles of an on-demand manufactured MUTANOME vaccine encoding the unique mutation signature of the individual patient identified by NGS. The mRNAs are administered intravenously as a RNA-lipoplex formulation which protects RNA from degradation, activates innate immunity, transfects APCs and consequently induces highly potent antigen-specific T-cell responses. Three clinical sites are open for recruitment; >12 patients were screened and vaccinations with WAREHOUSE or MUTANOME RNAs have started. We give insights into features of the established process and present first stratification data. MERIT was funded by the EU Commission’s FP7 and is led by BioNTech AG.
Clinical trial identification
Legal entity responsible for the study
European Commission’s FP7; BioNTech AG.
L. Heesen, K. Frenzel, S. Bolte, V. Bukur, E. Derhovanessian, S. Kreiter, A. Kuhn: Employment: BioNTech. M. Diken: Patent ownership, patent applications, employment: BioNTech AG. K. Kühlcke: Employment: BioNTech IMFS. T. Sjöblom: Founder, board member, shareholder: ExScale Biopecimen Solutions. A. Ö. Türeci: Co-founder: Ganymed Pharmaceuticals GmbH. U. Sahin: Patent ownership, patent applications, stock owner, management board member, co-founder: BioNTech AG; Co-founder, chair: TRON gGmbH; Membership on advisory board, co-founder: Ganymed Pharmaceuticals GmbH. All other authors have declared no conflicts of interest.