6O - IVAC MUTANOME – A first-in-human phase I clinical trial targeting individual mutant neoantigens for the treatment of melanoma (6O)

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Proffered Paper session
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Gastrointestinal Cancers
Presenter Matthias Miller
Citation Annals of Oncology (2017) 28 (suppl_11): xi1-xi2. 10.1093/annonc/mdx712
Authors M. Miller1, U. Sahin2, E. Derhovanessian3, B. Kloke4, P. Simon5, V. Bukur6, C. Albrecht7, A. Paruzynski6, M. Löwer8, A. Kuhn9, K. Schreeb10, S. Attig11, A. Kemmer Brueck10, S. Bolte10, S. Grabbe12, C. Höller13, J. Utikal14, C. Huber15, C. Loquai16, Ö. Türeci17
  • 1Project Management, Biopharmaceutical New Technologies (BioNTech) Corporation, 55131 - Mainz/DE
  • 2Management, Biopharmaceutical New Technologies (BioNTech) Corporation, Mainz/DE
  • 3Immunomonitoring, Biopharmaceutical New Technologies (BioNTech) Corporation, Mainz/DE
  • 4Project Management, Biopharmaceutical New Technologies (BioNTech) Corporation, Mainz/DE
  • 5Immunoreceptor Validation, Biopharmaceutical New Technologies (BioNTech) Corporation, Mainz/DE
  • 6Genomics, Biopharmaceutical New Technologies (BioNTech) Corporation, Mainz/DE
  • 7Genomics, TRON – Translational Oncology at the University Medical Center of Johannes Gutenberg University gGmbH, Mainz/DE
  • 8Bioinformatics, TRON – Translational Oncology at the University Medical Center of Johannes Gutenberg University gGmbH, Mainz/DE
  • 9Rna Biochemistry, Biopharmaceutical New Technologies (BioNTech) Corporation, Mainz/DE
  • 10Clinical Research, Biopharmaceutical New Technologies (BioNTech) Corporation, Mainz/DE
  • 11Immunmonitoring, TRON – Translational Oncology at the University Medical Center of Johannes Gutenberg University gGmbH, Mainz/DE
  • 12Dermatology, University Medical Center of the Johannes Gutenberg University, Mainz/DE
  • 13Dermatology, Medical University of Vienna, Vienna/AT
  • 14Dermatology, German Cancer Research Center (dkfz), Heidelberg/DE
  • 15Advisory Board, Biopharmaceutical New Technologies (BioNTech) Corporation, Mainz/DE
  • 16Dermatology, University Medical Center of the Johannes Gutenberg University, 55131 - Mainz/DE
  • 17Management, CI3 (Cluster of Individualized Immunointervention, Mainz/DE

Abstract

Background

The genome of cancer cells is inherently instable promoting multiple genomic alterations and epigenetic changes. This process leads to a unique molecular profile of every given tumor. Recently, a series of independent reports revealed that neo-antigen specific T-cell responses are seminal for the clinical efficacy of immune checkpoint inhibitors. However, less than 1% of mutations appear to raise spontaneously occurring T-cell response in the tumor-bearing patient. Accordingly, only patients with a high burden of mutations profit from currently approved therapies. To overcome this restriction, the IVAC® MUTANOME, a highly potent personalized neo-antigen-encoding RNA vaccine approach, harnesses the individual patient’s mutation profile. To this aim, the individual mutation repertoire is identified by next-generation-sequencing and 10 potentially immunogenic mutated sequences per patient are selected. These are incorporated into a poly-epitopic RNA vaccine (IVAC MUTANOME®) that is tailored to activate and expand the individual patient’s T cells against the unique mutation signature.

Methods

A phase I first-in-human trial has been initiated in 2013 in patients with stage III and IV malignant melanoma (NCT02035956) to test this fully personalized RNA vaccine concept. The objective of this clinical trial is to study the feasibility, safety, tolerability, immunogenicity and the potential anti-tumoral activity of the IVAC® MUTANOME approach.

Results

As of November 2016, 13 patients were evaluable for the assessment of the safety profile and the induction of antigen-specific immune responses. Notably, in each and every patient a strong poly-neo-epitopic immune response against vaccine antigens was detected. Overall, 60% of the 125 selected neo-epitopes elicited a T-cell response. Simultaneously, no severe adverse drug reactions were reported and indications for clinical activity were observed.

Conclusions

Vaccination with IVAC® MUTANOME was very well tolerated. A high pharmacological activity of the vaccine was observed in all enrolled patients encouraging further clinical development.

Clinical trial identification

NCT02035956; First Posted: January 14, 2014

Legal entity responsible for the study

Biontech RNA Pharmaceuticals GmbH

Funding

CI3 cluster program of the German Federal Ministry of Education and Research (BMBF).

Disclosure

M. Miller, K. Schreeb, S. Bolte: Employee of BioNTech AG. U. Sahin: Stock owner and management board member of BioNTech group; Co-founder and CEO BioNTech AG, Mainz. Head of the Scientific Advisory Board of Ganymed Pharmaceuticals AG. E. Derhovanessian, B-P. Kloke, P. Simon, V. Bukur, C. Albrecht, A. Kuhn, A. Kemmer Brueck, A. Paruzynski: Employee of the BioNTech group. S. Grabbe: AbbVie: Advisory Board, Reimbursement of travel costs. BMS: Advisory Board, Honorarium (oral presentation), Reimbursement of travel costs. MSD: Advisory Board, Honorarium (oral presentation), Reimbursement of travel costs. OnkoZert: Honorarium (Auditor), Reimbursement of travel costs. Roche: Advisory Board, Honorarium (oral presentation), Reimbursement of travel costs. Sanofi-Pasteur-MSD: Advisory Board, Reimbursement of travel costs. Takeda: Reimbursement of travel costs. Novartis: Advisory Board, Reimbursement of travel costs. MedConcept: Honorarium (oral presentation), Reimbursement of travel costs. Beiersdorf: Honorarium (oral presentation), Reimbursement of travel costs. L'Oreal: Honorarium (oral presentation), Reimbursement of travel costs. Merck Sero: Advisory Board, Reimbursement of travel costs. C. Höller: Speaker for Amgen, BMS, MSD, Novartis, Roche; Advisor for Amgen, BMS, Incyte, MSD, Novartis, Pierre Fabre, Roche. Ö. Türeci: Co-founder of Ganymed Pharmaceuticals AG. Member of Scientific Advisory Board of BioNTech AG. J. Utikal: Member of advisory boards and on speakers’ bureaus: Amgen, BMS, GSK, MSD, Novartis, Roche. C. Huber: Co-founder, shareholder, advisor und deputy chairman supervisory board BioNTech. C. Loquai: Advisory board: Roche, Novartis, Pierre Fabre, MSD, BMS, Leo, Amgen, Biontech; Speekers fee: Roche, Novartis, Pierre Fabre, MSD, BMS, Amgen; Travel Reimbursement: Roche, Novartis, MSD, BMS, Amgen. All other authors have declared no conflicts of interest.