First-in-human study of the biodistribution and pharmacokinetics of 89Zr-CX-072, a novel immunopet tracer based on an anti–PD-L1 probody

Laura Kist de Ruijter, Jahlisa S. Hooiveld-Noeken, Danique Giesen, Marjolijn N. Lub-De Hooge, Iris C. Kok, Adrienne H. Brouwers, Sjoerd G. Elias, Margaret T.L. Nguyen, Hong Lu, Jourik A. Gietema, Mathilde Jalving, Derk J.A. de Groot, Olga Vasiljeva*, Elisabeth G.E. de Vries*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

23 Citations (Scopus)
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Purpose: 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 89Zr-CX-072 positron emission tomography (PET) imaging.

Experimental Design: Patients received 1 mg, 37 MBq 89Zr-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 (n ¼ 7) þ 3 mg/kg ipilimumab q3w 4 (n ¼ 1). Normal organ tracer uptake was expressed as standardized uptake value (SUV)mean and tumor uptake as SUVmax. PD-L1 expression was measured immunohistochemically in archival tumor tissue.

Results: Three of the eight patients included received 10-mg protein dose resulting in a blood pool mean SUVmean SD of 4.27 0.45 on day 4, indicating sufficient available tracer. Tumor uptake was highest at day 7, with a geometric mean SUVmax 5.89 (n ¼ 113) and present in all patients. The median follow-up was 12 weeks (4–76þ). 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 SUVmean 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.

Conclusions: 89Zr-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.

Original languageEnglish
Pages (from-to)5325-5333
Number of pages9
JournalClinical Cancer Research
Issue number19
Publication statusPublished - 1-Oct-2021


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