Tilsotolimod with ipilimumab drives tumor responses in anti–pd-1 refractory melanoma

Cara Haymaker, Daniel H. Johnson, Ravi Murthy, Salah Eddine Bentebibel, Marc I. Uemura, Courtney W. Hudgens, Houssein Safa, Marihella James, Robert H.I. Andtbacka, Douglas B. Johnson, Montaser Shaheen, Michael A. Davies, Shah Rahimian, Srinivas K. Chunduru, Denái R. Milton, Michael T. Tetzlaff, Willem W. Overwijk, Patrick Hwu, Nashat Gabrail, Sudhir AgrawalGary Doolittle, Igor Puzanov, Joseph Markowitz, Chantale Bernatchez, Adi Diab

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Many patients with advanced melanoma are resistant to immune checkpoint inhibi-tion. 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 IFNα 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.

Original languageEnglish (US)
Pages (from-to)1996-2013
Number of pages18
JournalCancer discovery
Volume11
Issue number8
DOIs
StatePublished - Aug 2021

ASJC Scopus subject areas

  • Oncology

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