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

Purpose: The stimulator of IFN genes (STING) is a transmem-brane protein that plays a role in the immune response to tumors. Single-agent STING agonist MIW815 (ADU-S100) has demon-strated 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 intra-tumoral injections of MIW815 (50-3,200 mu g) 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. Pharmacody-namic 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.

Automated summary

This study assessed the safety and tolerability of the combination of MIW815 and spartalizumab in patients with advanced solid tumors or lymphomas. The results showed that the combination therapy had immune activation but limited antitumor activity.