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

• Published in: Clinical cancer research Vol. 28; no. 4; pp. 677 - 688
• Main Authors: Meric-Bernstam, Funda, Sweis, Randy F, Hodi, F Stephen, Messersmith, Wells A, Andtbacka, Robert H I, Ingham, Matthew, Lewis, Nancy, Chen, Xinhui, Pelletier, Marc, Chen, Xueying, Wu, Jincheng, McWhirter, Sarah M, Müller, Thomas, Nair, Nitya, Luke, Jason J
• Format: Journal Article
• Language: English
• Published: United States 15.02.2022
• Subjects: Adult; Humans; Immunotherapy; Lymphoma; Maximum Tolerated Dose; Neoplasms - drug therapy; Neoplasms - pathology; Neoplasms, Second Primary
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-21-1963

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