University of California San Francisco United States
We have initiated the first-ever, proof-of-concept, translational study of gallium citrate PET as a non-invasive imaging biomarker of MYC activity for mCRPC patients receiving a next generation potent bromodomain 4 BRD4 inhibitor. Our preliminary results to date demonstrate that gallium citrate PET can feasibly detect metastatic lesions in patients with advanced prostate cancer, and that there are early signals that uptake on PET scan is associated with histologic evidence of small cellneuroendocrine differentiation, MYC overexpression, and amplification of MYC gene upon analysis of circulating tumor DNA. We have observed significant intra- and inter-patient heterogeneity of gallium citrate uptake on PET scan, which is likely reflective of the underlying biological heterogeneity of metastatic castration resistant prostate cancer. We have initiated paired gallium citrate PET imaging in patients being treated with BET bromodomain inhibitors, a class of therapies known to downregulate MYC expression. Study accrual is ongoing and interim analysis is planned within the next 6 months. Planned analyses include 1 correlation of gallium citrate uptake on PET with MYC copy number and expression levels, and 2 determination of the mean percent change from baseline in Ga-citrate uptake on PET upon treatment with BET bromodomain inhibitor treatment.