Phase I Dose-Escalation Trial of MIW815 (ADU-S100), an Intratumoral STING Agonist, in Patients with Advanced/Metastatic Solid Tumors or Lymphomas

  • Clin Cancer Res. 2022 Feb 15;28(4):677-688. doi: 10.1158/1078-0432.CCR-21-1963.
Funda Meric-Bernstam  1 ,  Randy F Sweis  2 ,  F Stephen Hodi  3 ,  Wells A Messersmith  4 ,  Robert H I Andtbacka  5 ,  Matthew Ingham  6 ,  Nancy Lewis  7 ,  Xinhui Chen  8 ,  Marc Pelletier  9 ,  Xueying Chen  9 ,  Jincheng Wu  9 ,  Sarah M McWhirter  10 ,  Thomas Müller  10 ,  Nitya Nair  10 ,  Jason J Luke  11
Affiliations
  • 1. Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
  • 2. The University of Chicago, Chicago, Illinois.
  • 3. Dana-Farber Cancer Institute, Boston, Massachusetts.
  • 4. University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
  • 5. Huntsman Cancer Institute, The University of Utah, Salt Lake City, Utah.
  • 6. Columbia University Irving Medical Center, New York, New York.
  • 7. Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
  • 8. Novartis Institutes for BioMedical Research, East Hanover, New Jersey.
  • 9. Novartis Institute for Biomedical Research, Cambridge, Massachusetts.
  • 10. Aduro Biotech, Inc., Berkeley, California.
  • 11. UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania.
PMID: 34716197 DOI: 10.1158/1078-0432.CCR-21-1963
Abstract

Purpose: This phase I study assessed the safety, pharmacokinetics (PKs), and efficacy of MIW815 (ADU-S100), a novel synthetic cyclic dinucleotide that activates the stimulator of IFN genes (STING) pathway, in patients with advanced/metastatic cancers.

Patients and methods: Patients (n = 47) received weekly i.t. injections of MIW815, 50 to 6,400 μg, on a 3-weeks-on/1-week-off schedule.

Results: A maximum tolerated dose was not reached. Most common treatment-related adverse events were pyrexia (17%), chills, and injection-site Pain (each 15%). MIW815 was rapidly absorbed from the injection site with dose-proportional PK, a rapid terminal plasma half-life (approximately 24 minutes), and high interindividual variability. One patient had a partial response (PR; Merkel cell carcinoma); two patients had unconfirmed PR (parotid Cancer, myxofibrosarcoma). Lesion size was stable or decreased in 94% of evaluable, injected lesions. RNA expression and immune infiltration assessments in paired tumor biopsies did not reveal significant on-treatment changes. However, increases in inflammatory cytokines and peripheral blood T-cell clonal expansion suggested systemic immune activation.

Conclusions: MIW815 was well tolerated in patients with advanced/metastatic cancers. Clinical activity of single-agent MIW815 was limited in this first-in-human study; however, evidence of systemic immune activation was seen.