First-in-human phase 1 study of RO7119929, an oral TLR7 agonist prodrug, in patients with advanced primary or metastatic liver cancers - PubMed
3 days ago
- #cytokine release syndrome
- #liver cancer
- #TLR7 agonist
- First-in-human phase 1 study of RO7119929, an oral TLR7 agonist prodrug, in patients with advanced primary or metastatic liver cancers.
- RO7119929 is converted to active drug predominantly in the liver, aiming to reprogram the local immune microenvironment.
- Preclinical results showed antitumor activity and proinflammatory proof-of-mechanism in mouse liver tumors and cynomolgus monkey liver tissue.
- The study enrolled 27 patients in flat-dose (FD) cohorts, 18 in FD expansion, and 9 in step-up dose (SUD) cohorts.
- Most common primary tumor type was hepatocellular carcinoma (HCC) (31%).
- Treatment-related adverse events (TRAEs) occurred in 91% of patients, with cytokine release syndrome (CRS) being the most common (81%).
- CRS was identified as a dose-limiting safety risk, with higher incidence and severity in FD cohorts.
- TLR7-related gene expression and cytokine induction was observed, indicating treatment-induced local inflammation of the tumor microenvironment.
- Among 17 HCC patients, one durable complete response and 10 stable disease cases were observed.
- SUD reduced CRS risk while maintaining pharmacodynamic effects, but single-agent activity was limited, suggesting need for combination therapy with checkpoint inhibitors.