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 - Funding Information:
The authors thank the patients and their families who participated in this clinical trial. Ted Everson, PhD, and Andy Johnson, DPhil, of Idera Pharmaceuticals, Inc. provided medical writing support. AOIC, LLC provided assistance with graphics, populating data tables, and editing. This support was funded by Idera Pharmaceuticals, Inc. This project was supported in part by the NCI through the Cancer Center Support Grant P30CA16672 (Institutional Tissue Bank and Research Histology Core Laboratory), the Translational Molecular Pathology– Immunoprofiling lab (TMP-IL) at the Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, the NCI Cooperative Agreement U24CA224285 (to the MD Anderson Cancer Center CIMAC), and the NCI grant award number P50CA221703 and philanthropic contributions to The University of Texas MD Anderson Cancer Center Melanoma Moon Shots Program (Melcore Lab).
Funding Information:
S. Rahimian and S.K. Chunduru are employees of Idera Pharmaceuticals, Inc. and own company stock. A. Diab received research funding and consultation fees from Idera Pharmaceuticals, Inc., Nektar Therapeutics; Bristol Myers Squibb; Jounce Therapeutics; Novartis Pharmaceuticals; CureVac, Merck, Apexigen, and Array BioPharma. C. Haymaker received consultation fees from Idera Pharmaceuticals and is on the advisory board for Briacell, Inc. D.B. Johnson received research funding from Bristol Myers Squibb and Incyte and is on the advisory board for Array Biopharma, Bristol Myers Squibb, Janssen, Iovance, Merck, and Novartis. R.H.I. Andtbacka is on the advisory board for Aduro, Merck, Novartis, OncoSec, Pfizer, and Takara Bio. M.A. Davies has served on advisory boards for BMS, GSK, Roche/Genentech, and Novartis and has been the PI of grants to his institution from GSK and Roche/Genentech. S. Agrawal owns stock options in Idera Pharmaceuticals. J. Markowitz is on the advisory board for Newlink Genetics, has served on an advisory board for Array Biopharma, and has been PI of grants/funding to his institution from Idera Pharmaceuticals, Morphogenesis Inc, Navigate Biop-harma, Merck, Macrogenics, and Reata Pharmaceuticals. The other authors declare no competing interests.
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 - http://www.scopus.com/inward/record.url?scp=85110797550&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85110797550&partnerID=8YFLogxK
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 -