Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancers, making it an imaging & therapeutic target of interest. The utility of the PSMA-targeted imaging agent 99mTc-EC0652 is being evaluated, along with biomarker analysis of circulating tumor cells (CTCs), in pts with mCRPC in a completed PSMA-targeted chemotherapeutic study. We now report the PSMA heterogeneity via CTC vs. imaging in the pt population treated to date.
A total of 51 pts evaluated at the time of the data cut had baseline CT & bone scans performed in addition to a 99mTc-EC0652 SPECT/CT as a measure of imaging-based PSMA expression. 41 of 51 pts provided pre-treatment blood samples evaluable for CTC biomarker analysis, which included PSMA expression & predicted genomic instability status (pGI). Images collected from pts were analyzed for both their PSMA+ status as well as sensitivity relative to conventional imaging.
41 of 51 pts (80.4%) had detectable CTCs in their samples prior to therapy while 32 of 38 (84.2%) of the analyzed paired on-therapy samples had CTCs after treatment. At baseline PSMA+ CTCs were found in 19 of 51 (37.2%) pts and overall was expressed on 33% (IQR 11.3% - 40.1%) of CTCs within each pt sample. 15 of 17 (88%) PSMA+ pt samples were also pGI+. 31 of the 51 pts (60.7%) of the pts had bone scan (BS) data available to analyze. 27 of the 51 pts had CT scan data available to analyze for nodal lesions. Concordance between Conventional Imaging & 99mTc-EC0652.Table: 842P
|99mTc- EC0652+||99mTc- EC0652-||BS+||BS-||CT+||CT -|
|Bone Lesion (770)||770 (100%)||0||587 (76.2%)||183 (23.8%)||N/A||N/A|
|Nodes >1.5cm (54)||48 (88.9%)||6 (11.1%)||N/A||N/A||54||N/A|
|Nodes <1.5cm (69)||69||N/A||N/A||N/A||N/A||N/A|
In this cohort, most pts had CTCs for assessment. The majority of pts with CTCs had PSMA-CTCs. The pts CTCs expressing PSMA accounted for a small percentage of the total CTCs observed. These PSMA+ CTCs had high pGI. Pts with CTCs had PSMA imagable disease, especially in bone. The discordance between CTCs & imaging illustrate the disease heterogeneity in regards to PSMA expression. These data should be considered in designing future PSMA-directed regimens.
Clinical trial identification
Legal entity responsible for the study
M.J. Morris, O. Sartor: Consultant: Endocyte. A. Armour, R. Messmann, M. Groaning: Employee: Endocyte. All other authors have declared no conflicts of interest.