Abstract 2069: Initial PET imaging and pharmacokinetic results from a Phase I/II study of Zr-89-labeled anti-STEAP1 antibody in metastatic castrate-resistant prostate cancer (mCRPC) patients
Authors: Carrasquillo Jorge A. , Danila Daniel C. , Beylergil Volkan , O'Donoghue Joseph A. , Cheal Sarah M. , Ruan Shutian , Pandit-Taskar Neeta , Fox Josef J. , Fleming Stephen E. , Zanzonico Pat B. , Ragupathi Govind , Lyashchenko Serge K. , William Simon P. , Larson Steven M. , Scher Howard I. , Fine Bernard M. , Morris Michael J. 
Published: May 2015

Abstract
Introduction: STEAP1 (Six Transmembrane Epithelial Antigen of Prostate 1) is a cell-surface therapeutic target overexpressed in 85% of prostate cancers. Zr-89 MSTP2109A, a humanized antibody targeting STEAP1 conjugated with desferrioxamine and radiolabeled with positron emitter Zr-89 (T1/2 78 h) was developed to enable imaging of STEAP1 expressing tumors.
Methods: To evaluate safety, pharmacokinetics (PK), biodistribution and tumor uptake a prospective Phase I/II PET imaging study in mCRPC patients is ongoing. Patients with STEAP1 positive immunohistochemistry (IHC) in archival tissue were studied following 5.0 + 0.2 mCi IV injection of Zr-89 MSTP2109A (immunoreactivity 96 + 2%) . PET/CT images were compared with contemporaneous bone, CT and when available FDG scan findings on a lesional basis.
Results: 15 patients have been studied. Two drug related adverse events included mild rigors and/or chills.
The first 6 patients were imaged at four timepoints over a 7 day period and showed that PET imaging tumor uptake increased over time and was optimal at 6d (range 5-9). Based on this, all subsequent patients were imaged on day 6. Median PK showed: Plasma concentration at zero time (Co) 28.2%ID/L; T1/2 beta 197.8h; volume of distribution 3.543L; clearance 19.7 ml/h.
All patients had definite Zr-89 MSTP2109A uptake in multiple sites of known disease (bone scan or CT standard-of-reference). All patients had bone and 7 had soft tissue metastases on Zr-89 MSTP2109A. In 10 patients, the Zr-89 MSTP2109A and bone scans detected a similar number of lesions; in 5 patients, the bone scan detected many more lesions. This discordance may represent treated non viable disease, as contemporaneous FDG PET scans tended to concur with the Zr-89 MSTP2109A scans rather than bone scans. In 4 of 7 pts Zr-89 MSTP2109A detected more soft tissue lesions than CT. The mean maximal standardized uptake values (SUVmax) in bone and soft tissue metastasis were 22.5 + 13.5 (range 4.4 to 59.3) and 16.4 + 5.6 (range 9.0 to 24.0) respectively. Correlation of tumor SUVmax and IHC is in progress. 11 of 15 patients underwent 11 biopsies within 30d of study (mean 18 + 9d), 7 were performed in PET positive sites after Zr-89 MSTP2109A imaging, 4 were performed prior to PET imaging; tumor was present in 10 of the 11 biopsies and they were all Zr-89 MSTP2109A positive.
Conclusion: Zr-89 MSTP2109A is well tolerated. It shows high and progressively increasing tumor contrast in patients with mCRPC. All sites biopsied (11/11) had increased Zr-89 MSTP2109A uptake, only one biopsy was negative for tumor. Given its excellent tumor uptake additional studies to further characterize Zr-89 MSTP2109A may be pursued, for example, selecting patients for STEAP1 directed therapies, assessing treatment response to STEAP1 directed therapy, or as an early biomarker for metastatic disease.
Citation Format: Jorge A. Carrasquillo, Daniel C. Danila, Volkan Beylergil, Joseph A. O'Donoghue, Sarah M. Cheal, Shutian Ruan, Neeta Pandit-Taskar, Josef J. Fox, Stephen E. Fleming, Pat B. Zanzonico, Govind Ragupathi, Serge K. Lyashchenko, Simon P. William, Steven M. Larson, Howard I. Scher, Bernard M. Fine, Michael J. Morris. Initial PET imaging and pharmacokinetic results from a Phase I/II study of Zr-89-labeled anti-STEAP1 antibody in metastatic castrate-resistant prostate cancer (mCRPC) patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2069. doi:10.1158/1538-7445.AM2014-2069