TY - JOUR
T1 - First-in-human study of the biodistribution and pharmacokinetics of 89Zr-CX-072, a novel immunopet tracer based on an anti–PD-L1 probody
AU - de Ruijter, Laura Kist
AU - Hooiveld-Noeken, Jahlisa S.
AU - Giesen, Danique
AU - Lub-De Hooge, Marjolijn N.
AU - Kok, Iris C.
AU - Brouwers, Adrienne H.
AU - Elias, Sjoerd G.
AU - Nguyen, Margaret T.L.
AU - Lu, Hong
AU - Gietema, Jourik A.
AU - Jalving, Mathilde
AU - de Groot, Derk J.A.
AU - Vasiljeva, Olga
AU - de Vries, Elisabeth G.E.
N1 - Funding Information:
We thank Dr. R. Boellaard for support PET analyses. S. Davur, E. Ureno, and S. Viswanathan (CytomX Therapeutics, Inc.) assisted with producing and characterizing clinical-grade 89Zr-CX-072. We thank the Clinical Development team of CytomX Therapeutics, Inc. (especially V. Huels, M. Will, and S. Yalamanchili) for the support of substudy design and execution. A research grant of CytomX Therapeutics, Inc. supported this study to the UMCG, Groningen, the Netherlands. The study drug CX-072 and control molecules were supplied by CytomX Therapeutics, Inc. (PROBODY is a U.S. registered trademark of CytomX Therapeutics, Inc.).
Publisher Copyright:
2021 American Association for Cancer Research
PY - 2021/10/1
Y1 - 2021/10/1
N2 - 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.
AB - 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.
U2 - 10.1158/1078-0432.CCR-21-0453
DO - 10.1158/1078-0432.CCR-21-0453
M3 - Article
C2 - 34253583
AN - SCOPUS:85117830005
SN - 1078-0432
VL - 27
SP - 5325
EP - 5333
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 19
ER -