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485 Long term results from a phase 1 trial of GEN-009, a personalized neoantigen vaccine, combined with PD-1 inhibition in advanced solid tumors
  1. Maura Gillison1,
  2. Mark Awad2,
  3. Przemyslaw Twardowski3,
  4. Ammar Sukari4,
  5. Melissa Johnson5,
  6. Rudy Lackner6,
  7. Mark Stein7,
  8. Arthur DeCillis8,
  9. Richard Hernandez8,
  10. Jessica Price8,
  11. Kevin Mancini8,
  12. Mara Shainheit8,
  13. Gabriella Santone8,
  14. Syukri Shukor8,
  15. Ece Bicak8,
  16. Vijetha Vemulapalli8,
  17. Emily Tjon8,
  18. Jessica Flechtner8,
  19. Thomas Davis8 and
  20. Roger Cohen9
  1. 1MD Anderson Cancer Center, Houston, TX, USA
  2. 2Dana-Farber Cancer Institute, Boston, MA, USA
  3. 3John Wayne Cancer Institute, Duarte, CA, USA
  4. 4Karmanos Cancer Institute, Detroit, MI, USA
  5. 5Sarah Cannon Research Institute, Nashville, TN, USA
  6. 6University of Nebraska Medical Center, Omaha, NE, USA
  7. 7Columbia University Medical Center, New York City, NY, USA
  8. 8Genocea, Madison, CT, USA
  9. 9University of Pennsylvania, Philadelphia, PA, USA


Background GEN-009 adjuvanted personalized cancer vaccine contains up to 20 neoantigens selected by ATLAS™, an ex vivo bioassay screening autologous T-cells for immune responses against both neoantigens and Inhibigens™. Inhibigen-specific T-cells suppress immunity, have been shown to accelerate tumor progression in mice, and are excluded from GEN-009. In cohort A, all patients immunized in the adjuvant setting with GEN-009 monotherapy developed immune responses. Ninety-nine percent of selected peptides were immunogenic: ex vivo CD4+ and CD8+ fluorospot responses specific for 51% and 41% of immunized peptides, respectively.1 Six of 8 patients continue without progression with a median follow up >2 years.

Methods GEN-009 was administered to patients with advanced cancer who received standard-of-care (SOC) PD-1 inhibitor as monotherapy or in combination therapy during vaccine manufacturing. Five vaccine doses were administered over 24 weeks in combination with single agent anti-PD-1. Patients who progressed prior to vaccination received salvage therapy followed by GEN-009 in combination. Peripheral T-cell responses were measured by ex vivo and in vitro stimulated fluorospot assays. Circulating tumor (ct) DNA levels were evaluated in a subset of patients pre- and post-GEN-009 administration.

Results 15 patients received GEN-009 in combination with PD-1 inhibitor; 1 patient received GEN-009 monotherapy. Median number of neoantigens per vaccine was 14 (range 5–18). GEN-009-related adverse events were limited to vaccine injection site reactions, mild myalgias or fatigue. Sequential vaccination with GEN-009 had an additive effect on the magnitude of ex vivo T-cell responses, that persisted in some patients for 12+ months post first vaccine dose. An association between proportion of peptides eliciting significant cytokine responses and RECIST response is apparent. Epitope spread was detected in CD8+ T-cells from CPI-sensitive patients, but not refractory patients. Four patients who responded to PD-1 inhibition followed by disease stabilization then demonstrated further tumor reduction after GEN-009 vaccination. Seven of 9 CPI responsive patients are progression-free 7 to 18 months after first vaccine dose. Three of 7 CPI-refractory patients have experienced unexpected prolonged stable disease, with 2 PR and 1 SD after vaccination lasting up to 10 months. Plasma ctDNA kinetics mirrored RECIST responses in each tested patient; in some responders, all evidence of ctDNA disappeared, including non-targeted antigens.

Conclusions Vaccination with GEN-009 alone or in combination with anti-PD-1 was well tolerated. Preliminary data demonstrate induction of robust, durable neoantigen-specific immune responses and epitope spreading in the presence of PD-1 CPI. Broad immunity against tumor specific targets and encouraging patient outcomes support further study.

Trial Registration identifier: NCT03633110


  1. Lam H, et al. An empirical antigen selection method identifies neoantigens that either elicit broad anti-tumor response or drive tumor growth. Cancer Discovery 2021 March;11(3):696–713.

Ethics Approval This study was approved by Western Institutional Review Board, approval number 1-1078861-1

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