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

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