Skip NavigationSkip to Content
Return Return to Search Results

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

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

  2. Author Address

    Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA; Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: davard@upmc.edu., Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA; Department of Dermatology, University of Pittsburgh, Pittsburgh, PA, USA., Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA., Division of Dermatopathology, Johns Hopkins University, Baltimore, MD, USA., Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA; Genetics and Microbiome Core, Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA., University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA; Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA., Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA; Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA., University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA; Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA., University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA; Division of Surgical Oncology, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA., University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA; Division of Plastic Surgery, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA., Nanostring Technologies, Seattle, WA, USA., Checkmate Pharmaceuticals, Cambridge, MA, USA., Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA., Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Division of Dermatopathology, Johns Hopkins University, Baltimore, MD, USA; Tumor Microenvironment Core, Bloomberg-Kimmel Institute of Immunotherapy, Mark Foundation Center for Advanced Imaging and Genomics, Johns Hopkins University, Baltimore, MD, USA., Department of Dermatology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA., Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. Electronic address: trinchig@mail.nih.gov., Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA; Department of Dermatology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: zarourhm@upmc.edu.,
    1. Year: 2024
    2. Date: Oct 30
    3. Epub Date: 2024 10 30
  2. Journal: Cancer Cell
  4. Type of Article: Article
  1. 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+ tumor-infiltrating lymphocytes and plasmacytoid dendritic cells (pDCs) in the tumor microenvironment, and increased frequencies of Ki67+CD8+ 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. Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1016/j.ccell.2024.10.007
  3. PMID: 39486411
  4. PII : S1535-6108(24)00395-7

Library Notes

  1. Fiscal Year: FY2024-2025
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel