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
; 28(4): 677-688, 2022 02 15.
Article
em En
| MEDLINE
| ID: mdl-34716197
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 ANDMETHODS:
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Segunda Neoplasia Primária
/
Linfoma
/
Neoplasias
Limite:
Adult
/
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article