TY - JOUR
T1 - Tilsotolimod with ipilimumab drives tumor responses in anti–pd-1 refractory melanoma
AU - Haymaker, Cara
AU - Johnson, Daniel H.
AU - Murthy, Ravi
AU - Bentebibel, Salah Eddine
AU - Uemura, Marc I.
AU - Hudgens, Courtney W.
AU - Safa, Houssein
AU - James, Marihella
AU - Andtbacka, Robert H.I.
AU - Johnson, Douglas B.
AU - Shaheen, Montaser
AU - Davies, Michael A.
AU - Rahimian, Shah
AU - Chunduru, Srinivas K.
AU - Milton, Denái R.
AU - Tetzlaff, Michael T.
AU - Overwijk, Willem W.
AU - Hwu, Patrick
AU - Gabrail, Nashat
AU - Agrawal, Sudhir
AU - Doolittle, Gary
AU - Puzanov, Igor
AU - Markowitz, Joseph
AU - Bernatchez, Chantale
AU - Diab, Adi
N1 - Publisher Copyright:
© 2021 American Association for Cancer Research
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85110797550
UR - https://www.scopus.com/pages/publications/85110797550#tab=citedBy
U2 - 10.1158/2159-8290.CD-20-1546
DO - 10.1158/2159-8290.CD-20-1546
M3 - Article
C2 - 33707233
AN - SCOPUS:85110797550
SN - 2159-8274
VL - 11
SP - 1996
EP - 2013
JO - Cancer Discovery
JF - Cancer Discovery
IS - 8
ER -