Ott et al. reported the results of a single arm study of a personalized neoantigen vaccine (Neo-PV-01) in combination with anti-PD-1 therapy in advanced melanoma, lung, and bladder cancer patients. The combined treatment was safe and feasible, and radiographic and histologic measurements improved following vaccination and continued anti-PD-1 therapy. In the melanoma cohort, increased, TCR clonality, peripheral memory T cells, and TCF7+CD8+T cells in the TME correlated with lack of progression by 9 months. NEO-PV-01 plus nivolumab induced neoantigen-specific T cell reactivity, cytotoxicity, tumor infiltration, and epitope spreading.
Contributed by Shishir Pant
ABSTRACT: Neoantigens arise from mutations in cancer cells and are important targets of T cell-mediated anti-tumor im- munity. Here, we report the first open-label, phase Ib clinical trial of a personalized neoantigen-based vac- cine, NEO-PV-01, in combination with PD-1 blockade in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer. This analysis of 82 patients demonstrated that the regimen was safe, with no treatment-related serious adverse events observed. De novo neoantigen-specific CD4+ and CD8+ T cell responses were observed post-vaccination in all of the patients. The vaccine-induced immune cells had a cytotoxic phenotype and were capable of trafficking to the tumor and mediating cell killing. In addition, epitope spread to neoantigens not included in the vaccine was detected post-vaccination. These data sup- port the safety and immunogenicity of this regimen in patients with advanced solid tumors (Clinicaltrials.gov: NCT02897765).
Author Info: (1) Dana Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA (2) Department of Medicine, University of California, Los Angeles, Los A
Author Info: (1) Dana Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA (2) Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA (3) Washington University School of Medicine, St. Louis, MO, USA (4) Departments of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA (5) Tisch Cancer Institute, Icahn School of Medicine, New York, NY, USA (6) Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA (7) Memorial Sloan Kettering Cancer Center, New York, NY, USA (8) Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA (9) Department of Medicine, Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA, USA (10) Neon Therapeutics/BioNTech US, Cambridge, MA, USA (11) Lead Contact
*Correspondence: patrick_ott@dfci.harvard.edu (P.A.O.), lakshmi.srinivasan@biontech.us (L.S.)
