Safety, pharmacokinetics, pharmacodynamics, and antitumor activity of cergutuzumab amunaleukin: a phase I study in patients with advanced and/or metastatic solid tumors

BACKGROUND: Cergutuzumab amunaleukin (CA) is a novel immunocytokine comprising an interleukin-2 variant moiety with abolished CD25 (interleukin-2 receptor α) binding, fused to a bivalent anti-carcinoembryonic antigen (CEA) monoclonal antibody. This first-in-human phase I study evaluated the maximum tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamics, and antitumor activity of CA. MATERIAL AND METHODS: Patients had CEA-positive advanced and/or metastatic solid tumors that had progressed on standard-of-care treatment. The study consisted of two parts: patients received single-dose CA 0.1-6 mg (n = 5) in part I and multiple ascending doses of 10-40 mg every 2 weeks (q2w; n = 31) or 6-30 mg weekly (qw; n = 24) in part II. Patients with advanced renal cell carcinoma or melanoma (CEA-negative) were permitted in part II. RESULTS: ). There were no objective responses; 6/53 (11%) evaluable patients had stable disease (median duration 4.5 months). CONCLUSIONS: . Further development in combination with additional immunomodulatory agents is warranted.