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.

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.