Combination of the STING Agonist MIW815 (ADU-S100) and PD-1 Inhibitor Spartalizumab in Advanced/Metastatic Solid Tumors or Lymphomas: An Open-Label, Multicenter, Phase Ib Study
- Author(s)
- Meric-Bernstam, F; Sweis, RF; Kasper, S; Hamid, O; Bhatia, S; Dummer, R; Stradella, A; Long, GV; Spreafico, A; Shimizu, T; Steeghs, N; Luke, JJ; McWhirter, SM; Muller, T; Nair, N; Lewis, N; Chen, X; Bean, A; Kattenhorn, L; Pelletier, M; Sandhu, S;
- Journal Title
- Clinical Cancer Research
- Publication Type
- Research article
- Abstract
- 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 mug) 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.
- Publisher
- American Association for Cancer Research
- Keywords
- Humans; Immune Checkpoint Inhibitors/therapeutic use; *Neoplasms/pathology; *Lymphoma/drug therapy; *Neoplasms, Second Primary/drug therapy
- Department(s)
- Medical Oncology
- PubMed ID
- 36282874
- Publisher's Version
- https://doi.org/10.1158/1078-0432.CCR-22-2235
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-06-06 06:44:07
Last Modified: 2023-06-06 06:45:18