Data from A Phase I Pharmacokinetic and Biological Correlative Study of IMP321, a Novel MHC Class II Agonist, in Patients with Advanced Renal Cell Carcinoma

Abstract

<div>Abstract<p><b>Purpose:</b> To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of IMP321, a recombinant soluble LAG-3Ig fusion protein which agonizes MHC class II–driven dendritic cell activation.</p><p><b>Experimental Design:</b> Patients with advanced renal cell carcinoma were treated with escalating doses of IMP321 s.c. Blood samples were assayed to determine plasma pharmacokinetic parameters, detect human anti-IMP321 antibody formation, and determine long-lived CD8 T cell responses.</p><p><b>Results:</b> Twenty-one advanced renal cell carcinoma patients received 119 injections of IMP321 at doses ranging from 0.050 to 30 mg/injection s.c. biweekly for 6 injections. No clinically significant adverse events were observed. Good systemic exposure to the product was obtained following s.c. injections of doses above 6 mg. IMP321 induced both sustained CD8 T-cell activation and an increase in the percentage of long-lived effector-memory CD8 T cells in all patients at doses above 6 mg. Tumor growth was reduced and progression-free survival was better in those patients receiving higher doses (>6 mg) of IMP321: 7 of 8 evaluable patients treated at the higher doses experienced stable disease at 3 months compared with only 3 of 11 in the lower dose group (<i>P</i> = 0.015).</p><p><b>Conclusion:</b> The absence of toxicity and the demonstration of activity at doses above 6 mg warrant further disease-directed studies of IMP321 in combined regimens (e.g., chemoimmunotherapy). (Clin Cancer Res 2009;15(19):6225–31)</p></div>