Safety, pharmacokinetics, pharmacodynamics, and antitumor activity of cergutuzumab amunaleukin: a phase I study in patients with advanced and/or metastatic solid tumors - PubMed
3 hours ago
- #phase I trial
- #solid tumors
- #immunotherapy
- Cergutuzumab amunaleukin (CA) is an immunocytokine targeting CEA with an IL-2 variant lacking CD25 binding, evaluated in a first-in-human phase I trial for advanced/metastatic solid tumors.
- The study enrolled 60 patients with CEA-positive tumors; dosing included single doses (0.1-6 mg) and multiple ascending doses every 2 weeks (10-40 mg) or weekly (6-30 mg).
- Maximum tolerated dose (MTD) was established at 30 mg every 2 weeks, with dose-limiting toxicities including hypophosphatemia, thrombocytopenia, capillary leak syndrome, and fatigue.
- Common adverse events were pyrexia (68%) and infusion-related reactions (52%); pharmacokinetics showed target-mediated disposition with dose-proportional exposure at 6-40 mg.
- CA pharmacodynamically expanded CD8+ T cells and natural killer cells, but not regulatory T cells (Treg), aligning with its mechanism; no objective responses occurred, but 11% had stable disease.
- The safety profile was manageable, supporting further development in combination with other immunomodulatory agents for enhanced antitumor activity.