Data from First-in-Human Study of the Biodistribution and Pharmacokinetics of <sup>89</sup>Zr-CX-072, a Novel Immunopet Tracer Based on an Anti–PD-L1 Probody

Abstract

<div>AbstractPurpose:<p>CX-072, a PD-L1–targeting Probody therapeutic, is engineered to be activated by tumor proteases that remove a masking peptide. To study effects on biodistribution and pharmacokinetics, we performed <sup>89</sup>Zr-CX-072 positron emission tomography (PET) imaging.</p>Experimental Design:<p>Patients received ∼1 mg, 37 MBq <sup>89</sup>Zr-CX-072 plus 0, 4, or 9 mg unlabeled CX-072 and PET scans at days 2, 4, and 7. After that, treatment comprised 10 mg/kg CX-072 q2 weeks (<i>n</i> = 7) + 3 mg/kg ipilimumab q3w 4× (<i>n</i> = 1). Normal organ tracer uptake was expressed as standardized uptake value (SUV)<sub>mean</sub> and tumor uptake as SUV<sub>max</sub>. PD-L1 expression was measured immunohistochemically in archival tumor tissue.</p>Results:<p>Three of the eight patients included received 10-mg protein dose resulting in a blood pool mean SUV<sub>mean</sub> ± SD of 4.27 ± 0.45 on day 4, indicating sufficient available tracer. Tumor uptake was highest at day 7, with a geometric mean SUV<sub>max</sub> 5.89 (<i>n</i> = 113) and present in all patients. The median follow-up was 12 weeks (4–76+). One patient experienced stable disease and two patients a partial response. PD-L1 tumor expression was 90% in one patient and ≤1% in the other patients. Mean SUV<sub>mean</sub> ± SD day 4 at 10 mg in the spleen was 8.56 ± 1.04, bone marrow 2.21 ± 0.46, and liver 4.97 ± 0.97. Four patients out of seven showed uptake in normal lymph nodes and Waldeyer's ring. The tracer was intact in the serum or plasma.</p>Conclusions:<p><sup>89</sup>Zr-CX-072 showed tumor uptake, even in lesions with ≤1% PD-L1 expression, and modest uptake in normal lymphoid organs, with no unexpected uptake in other healthy tissues.</p></div>