Neoadjuvant vidutolimod and nivolumab in high-risk resectable melanoma: A prospective phase II trial

Intratumoral TLR9 agonists and anti-PD-1 produce clinical responses and broad immune activation. We conducted a single-arm study of neoadjuvant TLR9 agonist vidutolimod combined with anti-PD-1 nivolumab in high-risk resectable melanoma. In 31 evaluable patients, 55% major pathologic response (MPR) was observed, meeting primary endpoint. MPR was associated with necrosis, and melanophagocytosis with increased CD8<sup>+</sup> tumor-infiltrating lymphocytes and plasmacytoid dendritic cells (pDCs) in the tumor microenvironment, and increased frequencies of Ki67<sup>+</sup>CD8<sup>+</sup> T cells peripherally. MPRs had an enriched pre-treatment gene signature of myeloid cells, and response to therapy was associated with gene signatures of immune cells, pDCs, phagocytosis, and macrophage activation. MPRs gut microbiota were enriched for Gram-negative bacteria belonging to the Bacteroidaceae and Enterobacteriaceae families and the small subgroup of Gram-negative Firmicutes. Our findings support that combined vidutolimod and nivolumab stimulates a broad anti-tumor immune response and is associated with distinct baseline myeloid gene signature and gut microbiota. ClinicalTrials.gov identifier: NCT03618641.

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Publication Details

Journal
Cancer Cell
Published
2024-10-31
DOI
https://doi.org/10.1016/j.ccell.2024.10.007
Citations
45
Primary Topic
Cutaneous Melanoma Detection and Management
Type
article
Field-Weighted Citation Impact
12.71

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article

Neoadjuvant vidutolimod and nivolumab in high-risk resectable melanoma: A prospective phase II trial

David Mauro, Dmitri Bobilev, Lei Zhao, Arivarasan Karunamurthy et al.
45 citations
Cancer Cell
Cutaneous Melanoma Detection and Management
12.71
article

Neoadjuvant vidutolimod and nivolumab in high-risk resectable melanoma: A prospective phase II trial

David Mauro, Dmitri Bobilev, Lei Zhao, Arivarasan Karunamurthy, Robert M. Morrison, Douglas J. Hartman, Amanda G. Paulovich, John A. McCulloch, Ornella Pagliano, Christopher Deitrick, Hassane M. Zarour, Riyue Bao, Diwakar Davar, Alicia M. Cole, Janis M. Taube, Corey Urban, Miriam R. Fernandes, Florent Amatore, Matthew P. Holtzman, Amiran Dzutsev, Umamaheswar Duvvuri, Jennifer R. Fang, Haroon A. Choudry, James E. Wooldridge, Yana George Najjar, Jason J. Luke, Wentao Gao, Richard R. Rodrigues, Shaum Sridharan, Christopher Groetsch, Julie S. Deutsch, John M. Kirkwood, Matthew G. Fury, Jeffrey R. Whiteaker, Richelle DeBlasio, Giorgio Trinchieri, Poonam Aggarwal, Jonathan H. Badger, Prajan Divarkar, Jie Sun, Yang Jin, Hong Wang, Yulong Bai, Hyun Jung Park, Seungwon Kim, Jagjit Singh, Rodrigo X. Das Neves, Arthur Μ. Krieg, James F. Pingpank, Quanquan Ding, James Patrick O'Toole, Joe-Marc Chauvin, Amy Rose
article en
45 citations

Abstract

Intratumoral TLR9 agonists and anti-PD-1 produce clinical responses and broad immune activation. We conducted a single-arm study of neoadjuvant TLR9 agonist vidutolimod combined with anti-PD-1 nivolumab in high-risk resectable melanoma. In 31 evaluable patients, 55% major pathologic response (MPR) was observed, meeting primary endpoint. MPR was associated with necrosis, and melanophagocytosis with increased CD8<sup>+</sup> tumor-infiltrating lymphocytes and plasmacytoid dendritic cells (pDCs) in the tumor microenvironment, and increased frequencies of Ki67<sup>+</sup>CD8<sup>+</sup> T cells peripherally. MPRs had an enriched pre-treatment gene signature of myeloid cells, and response to therapy was associated with gene signatures of immune cells, pDCs, phagocytosis, and macrophage activation. MPRs gut microbiota were enriched for Gram-negative bacteria belonging to the Bacteroidaceae and Enterobacteriaceae families and the small subgroup of Gram-negative Firmicutes. Our findings support that combined vidutolimod and nivolumab stimulates a broad anti-tumor immune response and is associated with distinct baseline myeloid gene signature and gut microbiota. ClinicalTrials.gov identifier: NCT03618641.

Cancer CellVol. 42(11)
Johns Hopkins University (US), University of Pittsburgh (US), Regeneron (United States) (US), Johns Hopkins Medicine (US), Fred Hutch Cancer Center (US), Nanostring Technologies (United States) (US), UPMC Hillman Cancer Center (US), Frederick National Laboratory for Cancer Research (US), University of Pittsburgh Medical Center (US), National Cancer Institute (US), Center for Cancer Research (US)
Melanoma Research Alliance, University of Pennsylvania, University of Pittsburgh, Regeneron Pharmaceuticals, National Institutes of Health, Center for Research Computing, University of Pittsburgh, National Cancer Institute
Zero hunger
Openalex Percentile: Top 1%
Cutaneous Melanoma Detection and Management
12.71
DOIOpen Access PDFOpenAlex
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