Journal article
Overcoming PD-1 Blockade Resistance with CpG-A Toll-Like Receptor 9 Agonist Vidutolimod in Patients with Metastatic Melanoma
Cancer discovery, Vol.11(12), pp.2998-3007
12/01/2021
DOI: 10.1158/2159-8290.CD-21-0425
PMCID: PMC8799774
PMID: 34326162
Abstract
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.
In this phase Ib study in patients with advanced melanoma, intratumoral TLR9 agonist vidutolimod in combination with pembrolizumab had a manageable safety profile and showed promising clinical activity, supporting the further clinical development of vidutolimod to overcome PD-1 blockade resistance through induction of an IFN response. See related commentary by Sullivan, p. 2960. This article is highlighted in the In This Issue feature, p. 2945.
Details
- Title: Subtitle
- Overcoming PD-1 Blockade Resistance with CpG-A Toll-Like Receptor 9 Agonist Vidutolimod in Patients with Metastatic Melanoma
- Creators
- Antoni Ribas - University of California, Los AngelesTheresa Medina - University of Colorado Cancer CenterJohn M Kirkwood - University of PittsburghYousef Zakharia - University of IowaRene Gonzalez - University of Colorado Cancer CenterDiwakar Davar - University of PittsburghBartosz Chmielowski - University of California, Los AngelesKatie M Campbell - University of California, Los AngelesRiyue Bao - University of PittsburghHeather Kelley - Checkmate Pharmaceuticals, Inc., Cambridge, Massachusetts.Aaron Morris - Checkmate Pharmaceuticals, Inc., Cambridge, Massachusetts.David Mauro - Checkmate Pharmaceuticals, Inc., Cambridge, Massachusetts.James E Wooldridge - Checkmate Pharmaceuticals, Inc., Cambridge, Massachusetts.Jason J Luke - University of PittsburghGeorge J Weiner - University of IowaArthur M Krieg - Checkmate Pharmaceuticals, Inc., Cambridge, Massachusetts.Mohammed M Milhem - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Cancer discovery, Vol.11(12), pp.2998-3007
- DOI
- 10.1158/2159-8290.CD-21-0425
- PMID
- 34326162
- PMCID
- PMC8799774
- NLM abbreviation
- Cancer Discov
- ISSN
- 2159-8274
- eISSN
- 2159-8290
- Grant note
- T32 CA009120 / NCI NIH HHS R35 CA197633 / NCI NIH HHS P30 CA086862 / NCI NIH HHS P01 CA244118 / NCI NIH HHS
- Language
- English
- Date published
- 12/01/2021
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
- Record Identifier
- 9984359836602771
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