Awad et al. demonstrated that a personalized neoantigen vaccine, NEO-PV-01, in combination with anti-PD-1 and chemo as first-line therapy for advanced non-squamous NSCLC was well tolerated, without any serious treatment-related adverse events. Pre-treatment T cell infiltration into the TME, HLA class-II gene expression, and TCR diversity correlated with clinical response. Post-vaccine tumor biopsies showed increase in CD4+ T cell infiltration with effector and cytotoxic phenotypes. NEO-PV-01 combination therapy induced neoepitope-specific, persistent, and cytotoxic T cell responses, along with non-vaccinated epitope spread to KRAS and other mutations.
Contributed by Shishir Pant
ABSTRACT: Neoantigens arising from mutations in tumor DNA provide targets for immune-based therapy. Here, we report the clinical and immune data from a Phase Ib clinical trial of a personalized neoantigen-vaccine NEO-PV-01 in combination with pemetrexed, carboplatin, and pembrolizumab as first-line therapy for advanced non-squamous non-small cell lung cancer (NSCLC). This analysis of 38 patients treated with the regimen demonstrated no treatment-related serious adverse events. Multiple parameters including baseline tumor immune infiltration and on-treatment circulating tumor DNA levels were highly correlated with clinical response. De novo neoantigen-specific CD4(+) and CD8(+) T cell responses were observed post-vaccination. Epitope spread to non-vaccinating neoantigens, including responses to KRAS G12C and G12V mutations, were detected post-vaccination. Neoantigen-specific CD4(+) T cells generated post-vaccination revealed effector and cytotoxic phenotypes with increased CD4(+) T cell infiltration in the post-vaccine tumor biopsy. Collectively, these data support the safety and immunogenicity of this regimen in advanced non-squamous NSCLC.
Author Info: (1) Dana Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. (2) Washington University School of Medicine, St. Louis, MO, USA. (3) BioNT
Author Info: (1) Dana Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. (2) Washington University School of Medicine, St. Louis, MO, USA. (3) BioNTech US, Cambridge, MA, USA. (4) Tennessee Oncology, Nashville, TN, USA. (5) David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. (6) BioNTech US, Cambridge, MA, USA. (7) BioNTech US, Cambridge, MA, USA. (8) BioNTech US, Cambridge, MA, USA. (9) BioNTech US, Cambridge, MA, USA. (10) BioNTech US, Cambridge, MA, USA. (11) BioNTech US, Cambridge, MA, USA. (12) BioNTech US, Cambridge, MA, USA. (13) BioNTech US, Cambridge, MA, USA. (14) David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. (15) BioNTech US, Cambridge, MA, USA. (16) Natera, Austin, TX, USA. (17) BioNTech US, Cambridge, MA, USA. (18) BioNTech US, Cambridge, MA, USA. (19) BioNTech US, Cambridge, MA, USA. (20) BioNTech US, Cambridge, MA, USA. (21) BioNTech US, Cambridge, MA, USA. (22) BioNTech US, Cambridge, MA, USA. (23) BioNTech US, Cambridge, MA, USA. Electronic address: richard.gaynor@biontech.us. (24) BioNTech US, Cambridge, MA, USA. Electronic address: lakshmi.srinivasan1@external.biontech.us.
