88MO - T-cell responses induced by an individualized neoantigen specific immune therapy in post (neo)adjuvant patients with triple negative breast cancer

Background

Triple negative breast cancer (TNBC) presents with an aggressive clinical phenotype lacking expression of conventional drug targets. Overall survival in early- and advanced-stage disease is poor.

Methods

TNBC-MERIT is a phase I trial (NCT02316457) assessing the feasibility, safety and immunogenicity of a liposome-formulated intravenous RNA vaccine encoding different tumor antigen categories in TNBC patients after surgery and (neo-)adjuvant chemotherapy. Patients in two arms of this trial received a personalized set of pre-manufactured non-mutated shared tumor-associated antigens with or without universal T helper epitopes. In a third arm, patients were vaccinated with IVAC_M_uID, an on-demand manufactured Individualized NeoAntigen Specific Immunotherapy (iNeST) encoding neoepitopes derived from up to 20 cancer mutations determined by NGS. This report provides a preliminary data analysis of immune responses in IVAC_M_uID-vaccinated patients as analyzed by IFNγ-ELISpot, multimer staining, TCR repertoire profiling and single cell TCR sequencing (data final mid-2020).

Results

Immunogenicity data was generated from all 14 IVAC_M_uID-treated patients. All analyzed patients had vaccine-induced CD4⁺ and/or CD8⁺ T-cell responses against 1 to 10 of the vaccine neoepitopes detected by IFNγ ELISpot, ex vivo or after in vitro stimulation. A substantial number of T-cell responses against individual neoepitopes were induced de novo and of high magnitude (up to 10.3% of peripheral CD8 T cells). One of the index patients characterized in more detail mounted CD4⁺ and/or CD8⁺ T-cell responses against 10 of 20 vaccine neoepitopes. The highly poly-epitopic TCR-clonotype diversified CD8⁺ T-cell response comprised in aggregate about 30% of total peripheral CD8⁺ T cells and was sustained at high levels for at least 6 months after the last vaccination. Vaccine-induced CD8⁺ T cells were of effector/memory, PD1⁺ phenotype, with a high fraction IFNγ/TNFα/Mip-1a&b triple-positive.

Conclusions

This preliminary data suggests that the iNeST IVAC_M_uID is highly efficient in inducing strong poly-epitopic T-cell responses in patients with TNBC in the post-(neo) adjuvant setting.

Clinical trial identification

NCT02316457.

Editorial acknowledgement

Legal entity responsible for the study

BioNTech SE.

Funding

BioNTech SE.

Disclosure

M. Schmidt: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Research grant/Funding (self): BioNTech SE; Research grant/Funding (self): Genentech. I. Vogler: Full/Part-time employment: BioNTech RNA Pharmaceuticals GmbH. E. Derhovanessian: Full/Part-time employment: BioNTech SE. T. Omokoko: Full/Part-time employment: BioNTech Cell & Gene Therapies GmbH. E. Godehardt: Full/Part-time employment: BioNTech RNA Pharmaceuticals GmbH. A. Cortini: Full/Part-time employment: BioNTech Cell & Gene Therapies GmbH. S. Newrzela: Full/Part-time employment: BioNTech Cell & Gene Therapies GmbH. J. Grützner: Full/Part-time employment: BioNTech SE. S. Bolte: Full/Part-time employment: BioNTech SE. D. Langer: Full/Part-time employment: BioNTech SE. T. Sjöblom: Shareholder/Stockholder/Stock options, Officer/Board of Directors: Exscale Biospecimen Solution A. Ö. Türeci: Leadership role, Officer/Board of Directors: BioNTech SE. U. Sahin: Leadership role, Officer/Board of Directors: BioNTech SE. All other authors have declared no conflicts of interest.