Combination of the STING Agonist MIW815 and PD-1 Inhibitor Spartalizumab in Advanced/Metastatic Solid Tumors or Lymphomas: An Open-label, Multicenter, Phase Ib Study.

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, Müller T, Nair N, Lewis N, Chen X, Bean A, Kattenhorn L, Pelletier M, Sandhu S. Clin Cancer Res. 2022 Oct 25:CCR-22-2235. doi: 10.1158/1078-0432.CCR-22-2235. Epub ahead of print. PMID: 36282874.

Abstract

Purpose: The Stimulator of Interferon 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 anti-tumor activity. This Phase Ib, multi-center,dose-escalation study assessed the safety and tolerability of MIW815 plus spartalizumab (PDR001), a humanised 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(50-3200 μg) on a 3-weeks-on/1-week-off schedule or once every four weeks, plus a fixed dose of spartalizumab (400mg) 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 maximum tolerated dose 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 anti-tumor responses were seen.

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