Quemliclustat and chemotherapy with or without zimberelimab in metastatic pancreatic adenocarcinoma: a randomized phase 1 trial - PubMed
8 hours ago
- #Clinical Trial
- #Immunotherapy
- #Pancreatic Cancer
- Quemliclustat, a CD73 inhibitor, was evaluated in combination with gemcitabine/nab-paclitaxel (G/nP) with or without zimberelimab (anti-PD-1) in a phase 1b trial (ARC-8) for first-line metastatic pancreatic ductal adenocarcinoma.
- The study involved dose-escalation and expansion phases, enrolling a total of 138 patients, with primary endpoints focused on safety and tolerability, showing profiles consistent with G/nP.
- Clinical response rates and survival outcomes were encouraging, with high tumor NR4A expression linked to improved overall survival in ARC-8, but not in external cohorts from PRINCE or Morpheus-PDAC trials.
- Spatial tissue analyses indicated low activated T cells near high NR4A1 expression areas, suggesting an immunosuppressed tumor microenvironment.
- Maximal downregulation of NR4A expression post-treatment correlated with T cell activation and improved overall survival, highlighting a biological connection between adenosine suppression and clinical benefit.