Open AccessOvercoming PD-1 Blockade Resistance with CpG-A Toll-Like Receptor 9 Agonist Vidutolimod in Patients with Metastatic Melanoma
Author(s) -
Antoni Ribas,
Theresa Medina,
John M. Kirkwood,
Yousef Zakharia,
René González,
Diwakar Davar,
Bartosz Chmielowski,
Katie M. Campbell,
Riyue Bao,
Heather Kelley,
Aaron J Morris,
David Mauro,
James E. Wooldridge,
Jason J. Luke,
George J. Weiner,
Arthur Μ. Krieg,
Mohammed Milhem
Publication year - 2021
Publication title -
cancer discovery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.795
H-Index - 163
eISSN - 2159-8290
pISSN - 2159-8274
DOI - 10.1158/2159-8290.cd-21-0425
Subject(s) - pembrolizumab , medicine , blockade , tlr9 , agonist , melanoma , immune checkpoint , oncology , nivolumab , progressive disease , cancer , immunology , immunotherapy , cancer research , disease , receptor , biology , biochemistry , gene expression , dna methylation , gene
Patients with advanced melanoma that is resistant to PD-1 blockade therapy have limited treatment options. Vidutolimod (formerly CMP-001), a virus-like particle containing a CpG-A Toll-like receptor 9 (TLR9) agonist, may reverse PD-1 blockade resistance by triggering a strong IFN response to induce and attract antitumor T cells. In the dose-escalation part of this phase Ib study, vidutolimod was administered intratumorally at escalating doses with intravenous pembrolizumab to 44 patients with advanced melanoma who had progressive disease or stable disease on prior anti-PD-1 therapy. The combination of vidutolimod and pembrolizumab had a manageable safety profile, and durable responses were observed in 25% of patients, with tumor regression in both injected and noninjected lesions, including visceral lesions. Patients who responded to vidutolimod and pembrolizumab had noninflamed tumors at baseline and induction of an IFNγ gene signature following treatment, as well as increased systemic expression of the IFN-inducible chemokine CXCL10.