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

  • Clin Cancer Res. 2023 Jan 4;29(1):110-121. doi: 10.1158/1078-0432.CCR-22-2235.
Funda Meric-Bernstam  1 ,  Randy F Sweis  2 ,  Stefan Kasper  3 ,  Omid Hamid  4 ,  Shailender Bhatia  5 ,  Reinhard Dummer  6 ,  Agostina Stradella  7 ,  Georgina V Long  8 ,  Anna Spreafico  9 ,  Toshio Shimizu  10 ,  Neeltje Steeghs  11 ,  Jason J Luke  12 ,  Sarah M McWhirter  13 ,  Thomas Müller  13 ,  Nitya Nair  13 ,  Nancy Lewis  14 ,  Xinhui Chen  15 ,  Andrew Bean  14 ,  Lisa Kattenhorn  16 ,  Marc Pelletier  16 ,  Shahneen Sandhu  17
Affiliations
  • 1. The University of Texas MD Anderson Cancer Center, Houston, Texas.
  • 2. The University of Chicago, Chicago, Illinois.
  • 3. University Hospital Essen, West German Cancer Center, Essen, Germany.
  • 4. The Angeles Clinic and Research Institute, A Cedars Sinai Affiliate, Los Angeles, California.
  • 5. University of Washington, Seattle, Washington.
  • 6. Universitaetsspital Zuerich Dermatology, Zurich, Switzerland.
  • 7. Institut Català d'Oncologia - Hospital Duran i Reynals, L'Hospitalet de Llobregat, Catalunya, Spain.
  • 8. Melanoma Institute Australia, The University of Sydney, and Mater and Royal North Shore Hospitals, Sydney, Australia.
  • 9. Princess Margaret Cancer Centre, Toronto, Canada.
  • 10. National Cancer Center Hospital, Tokyo, Japan.
  • 11. Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • 12. The University of Pittsburgh, Pittsburgh, Pennsylvania.
  • 13. Aduro Biotech, Inc., Berkeley, California.
  • 14. Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
  • 15. Novartis Institutes for BioMedical Research, East Hanover, New Jersey.
  • 16. Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
  • 17. Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Australia.
PMID: 36282874 DOI: 10.1158/1078-0432.CCR-22-2235
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 μg) 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.