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dc.contributor.authorHaymaker, Cara
dc.contributor.authorAgrawal, Sudhir
dc.contributor.authorBernatchez, Chantale
dc.contributor.authorDiab, Adi
dc.date2022-08-11T08:10:01.000
dc.date.accessioned2022-08-23T16:52:32Z
dc.date.available2022-08-23T16:52:32Z
dc.date.issued2021-08-11
dc.date.submitted2022-02-15
dc.identifier.citation<p>Haymaker C, Johnson DH, Murthy R, Bentebibel SE, Uemura MI, Hudgens CW, Safa H, James M, Andtbacka RHI, Johnson DB, Shaheen M, Davies MA, Rahimian S, Chunduru SK, Milton DR, Tetzlaff MT, Overwijk WW, Hwu P, Gabrail N, Agrawal S, Doolittle G, Puzanov I, Markowitz J, Bernatchez C, Diab A. Tilsotolimod with Ipilimumab Drives Tumor Responses in Anti-PD-1 Refractory Melanoma. Cancer Discov. 2021 Aug;11(8):1996-2013. doi: 10.1158/2159-8290.CD-20-1546. Epub 2021 Mar 11. PMID: 33707233; PMCID: PMC8544022. <a href="https://doi.org/10.1158/2159-8290.CD-20-1546">Link to article on publisher's site</a></p>
dc.identifier.issn2159-8274 (Linking)
dc.identifier.doi10.1158/2159-8290.CD-20-1546
dc.identifier.pmid33707233
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42072
dc.description<p>Full author list omitted for brevity. For the full list of authors, see article.</p>
dc.description.abstractMany patients with advanced melanoma are resistant to immune checkpoint inhibition. In the ILLUMINATE-204 phase I/II trial, we assessed intratumoral tilsotolimod, an investigational Toll-like receptor 9 agonist, with systemic ipilimumab in patients with anti-PD-1- resistant advanced melanoma. In all patients, 48.4% experienced grade 3/4 treatment-emergent adverse events. The overall response rate at the recommended phase II dose of 8 mg was 22.4%, and an additional 49% of patients had stable disease. Responses in noninjected lesions and in patients expected to be resistant to ipilimumab monotherapy were observed. Rapid induction of a local IFNalpha gene signature, dendritic cell maturation and enhanced markers of antigen presentation, and T-cell clonal expansion correlated with clinical response. A phase III clinical trial with this combination (NCT03445533) is ongoing. SIGNIFICANCE: Despite recent developments in advanced melanoma therapies, most patients do not experience durable responses. Intratumoral tilsotolimod injection elicits a rapid, local type 1 IFN response and, in combination with ipilimumab, activates T cells to promote clinical activity, including in distant lesions and patients not expected to respond to ipilimumab alone. This article is highlighted in the In This Issue feature, p. 1861.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=33707233&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544022/
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectCancer Biology
dc.subjectNeoplasms
dc.titleTilsotolimod with Ipilimumab Drives Tumor Responses in Anti-PD-1 Refractory Melanoma
dc.typeJournal Article
dc.source.journaltitleCancer discovery
dc.source.volume11
dc.source.issue8
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/4875
dc.identifier.contextkey28209059
html.description.abstract<p>Many patients with advanced melanoma are resistant to immune checkpoint inhibition. In the ILLUMINATE-204 phase I/II trial, we assessed intratumoral tilsotolimod, an investigational Toll-like receptor 9 agonist, with systemic ipilimumab in patients with anti-PD-1- resistant advanced melanoma. In all patients, 48.4% experienced grade 3/4 treatment-emergent adverse events. The overall response rate at the recommended phase II dose of 8 mg was 22.4%, and an additional 49% of patients had stable disease. Responses in noninjected lesions and in patients expected to be resistant to ipilimumab monotherapy were observed. Rapid induction of a local IFNalpha gene signature, dendritic cell maturation and enhanced markers of antigen presentation, and T-cell clonal expansion correlated with clinical response. A phase III clinical trial with this combination (NCT03445533) is ongoing.</p> <p>SIGNIFICANCE: Despite recent developments in advanced melanoma therapies, most patients do not experience durable responses. Intratumoral tilsotolimod injection elicits a rapid, local type 1 IFN response and, in combination with ipilimumab, activates T cells to promote clinical activity, including in distant lesions and patients not expected to respond to ipilimumab alone. This article is highlighted in the In This Issue feature, p. 1861.</p>
dc.identifier.submissionpathoapubs/4875
dc.contributor.departmentDepartment of Medicine
dc.source.pages1996-2013


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