TY - JOUR
T1 - Combination of the STING Agonist MIW815 (ADU-S100) and PD-1 Inhibitor Spartalizumab in Advanced/ Metastatic Solid Tumors or Lymphomas
T2 - An Open-Label, Multicenter, Phase Ib Study
AU - Meric-Bernstam, Funda
AU - Sweis, Randy F.
AU - Kasper, Stefan
AU - Hamid, Omid
AU - Bhatia, Shailender
AU - Dummer, Reinhard
AU - Stradella, Agostina
AU - Long, Georgina V.
AU - Spreafico, Anna
AU - Shimizu, Toshio
AU - Steeghs, Neeltje
AU - Luke, Jason J.
AU - McWhirter, Sarah M.
AU - Müller, Thomas
AU - Nair, Nitya
AU - Lewis, Nancy
AU - Chen, Xinhui
AU - Bean, Andrew
AU - Kattenhorn, Lisa
AU - Pelletier, Marc
AU - Sandhu, Shahneen
N1 - Publisher Copyright:
©2022 American Association for Cancer Research.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - Purpose: The stimulator of IFN genes (STING) is a transmembrane protein that plays a role in the immune response to tumors. Single-agent STING agonist MIW815 (ADU-S100) has demonstrated immune activation but limited antitumor activity. This phase Ib, multicenter, dose-escalation study assessed the safety and tolerability of MIW815 plus spartalizumab (PDR001), a humanized IgG4 antibody against PD-1, in 106 patients with advanced solid tumors or lymphomas. Patients and Methods: Patients were treated with weekly intratumoral injections of MIW815 (50–3,200 mg) on a 3-weeks-on/1-week-off schedule or once every 4 weeks, plus a fixed dose of spartalizumab (400 mg) intravenously every 4 weeks. Results: Common adverse events were pyrexia (n = 23; 22%), injection site pain (n = 21; 20%), and diarrhea (n = 12; 11%). Overall response rate was 10.4%. The MTD was not reached. Pharmacodynamic biomarker analysis demonstrated on-target activity. Conclusions: The combination of MIW815 and spartalizumab was well tolerated in patients with advanced/metastatic cancers, including in patients with anti-PD-1 refractory disease. Minimal antitumor responses were seen.
AB - Purpose: The stimulator of IFN genes (STING) is a transmembrane protein that plays a role in the immune response to tumors. Single-agent STING agonist MIW815 (ADU-S100) has demonstrated immune activation but limited antitumor activity. This phase Ib, multicenter, dose-escalation study assessed the safety and tolerability of MIW815 plus spartalizumab (PDR001), a humanized IgG4 antibody against PD-1, in 106 patients with advanced solid tumors or lymphomas. Patients and Methods: Patients were treated with weekly intratumoral injections of MIW815 (50–3,200 mg) on a 3-weeks-on/1-week-off schedule or once every 4 weeks, plus a fixed dose of spartalizumab (400 mg) intravenously every 4 weeks. Results: Common adverse events were pyrexia (n = 23; 22%), injection site pain (n = 21; 20%), and diarrhea (n = 12; 11%). Overall response rate was 10.4%. The MTD was not reached. Pharmacodynamic biomarker analysis demonstrated on-target activity. Conclusions: The combination of MIW815 and spartalizumab was well tolerated in patients with advanced/metastatic cancers, including in patients with anti-PD-1 refractory disease. Minimal antitumor responses were seen.
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U2 - 10.1158/1078-0432.CCR-22-2235
DO - 10.1158/1078-0432.CCR-22-2235
M3 - Article
C2 - 36282874
AN - SCOPUS:85145491898
SN - 1078-0432
VL - 29
SP - 110
EP - 121
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 1
ER -