T Cell Responses to Individualized Neoantigen Therapy mRNA-4157 (V940) Alone or in Combination With Pembrolizumab in the Phase 1 KEYNOTE-603 Study

Justin F. Gainor, Massachusetts General Hospital, Boston, MA, United States.
Manish R. Patel, Florida Cancer Specialists/Sarah Cannon Research Institute, Sarasota, FL, United States.
Jeffrey S. Weber, NYU Langone Medical Center, New York, NY, United States.
Martin Gutierrez, Hackensack University Medical Center, Hackensack, NJ, United States.
Julie E. Bauman, George Washington University, Washington, DC, United States.
Jeffrey M. Clarke, Duke Medical Center, Durham, NC, United States.
Ricklie Julian, University of Arizona Cancer Center, Tucson, AZ, United States.
Aaron J. Scott, Banner University of Arizona Cancer Center, Tucson, AZ, United States.
Jessica L. Geiger, Cleveland Clinic, Cleveland, PH, United States.
Kedar Kirtane, Moffitt Cancer Center, Tampa, Florida, United States.
Celine Robert-Tissot, Moderna, Inc., Cambridge, MA, United States.
Brandon Coder, Moderna, Inc., Cambridge, MA, United States.
Moomal Tasneem, Moderna, Inc., Cambridge, MA, United States.
Jing Sun, Moderna, Inc., Cambridge, MA, United States.
Wei Zheng, Moderna, Inc., Cambridge, MA, United States.
Lauren Gerbereux, Moderna, Inc., Cambridge, MA, United States.
Andressa Laino, Moderna, Inc., Cambridge, MA, United States.
Filippos Porichis, Moderna, Inc., Cambridge, MA, United States.
Jack Russella Pollard, HiFiBiO Therapeutics, Cambridge, MA, United States.
Peijie Hou, Moderna, Inc., Cambridge, MA, United States.
Vasudha Sehgal, Moderna, Inc., Cambridge, MA, United States.
Xing Chen, Moderna, Inc., Cambridge, MA, United States.
Manju Morrissey, Moderna, Inc., Cambridge, MA, United States.
Hikmat N. Daghestani, Moderna, Inc., Cambridge, MA, United States.
Igor Feldman, Moderna, Inc., Cambridge, MA, United States.
Lakshmi Srinivasan, Moderna Therapeutics (United States), Cambridge, MA, United States.
Joshua P. Frederick, Moderna Inc., Cambridge, MA, United States.
Michelle Brown, Moderna, Inc., Cambridge, MA, United States.
Praveen Aanur, Moderna, Inc., Cambridge, MA, United States.
Robert Meehan, Moderna, Inc., Boston, MA, United States.
Howard A. Burris, Sarah Cannon Research Institute, Nashville, TN, United States.

Document Type

Journal Article

Publication Date

8-8-2024

Journal

Cancer discovery

DOI

10.1158/2159-8290.CD-24-0158

Abstract

mRNA-4157 (V940) is an individualized neoantigen therapy (INT) targeting up to 34 patient-specific tumor neoantigens to induce T cell responses and potentiate anti-tumor activity. We report mechanistic insights into the immunogenicity of mRNA-4157 via characterization of T cell responses to neoantigens from the first-in-human phase 1, KEYNOTE-603 study (NCT03313778) in patients with resected non-small cell lung cancer (Part A: 1mg mRNA-4157, n = 4) or resected cutaneous melanoma (Part D: 1mg mRNA-4157 + 200mg pembrolizumab, n = 12). Safety, tolerability, and immunogenicity were assessed. All patients experienced ≥1 treatment-emergent adverse event (AE); there were no grade 4/5 AEs or dose-limiting toxicities. mRNA-4157 alone induced consistent de novo, and strengthened pre-existing, T cell responses to targeted neoantigens. Following combination therapy, sustained mRNA-4157-induced neoantigen-specific T cell responses and expansion of cytotoxic CD8 and CD4 T cells were observed. These findings show the potential of a novel mRNA INT approach in oncology.

Department

Medicine

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