A phase II study of lutetium-177 DOTATATE in metastatic prostate cancer with neuroendocrine differentiation.

Abstract

TPS292 Background: Neuroendocrine differentiated prostate cancer (NED PCa) is an aggressive form of prostate cancer with few treatment options and a poor prognosis. There is evidence that NED PCa and advanced castration resistant prostate cancers (CRPC) overexpress the somatostatin receptor (SSTR), which can be targeted with Lu-177 DOTATATE, a radiopharmaceutical therapy that improves survival in neuroendocrine tumors of the midgut. We are conducting a phase II trials investigating Lu-177 DOTATATE in NED PCa. Methods: This is a phase II trial run through the National Cancer Institute’s (NCI) Experimental Therapeutics Clinical Trials Network (ETCTN). Key inclusion criteria include evidence of neuroendocrine differentiation by histology (i.e. small cell carcinoma or positivity for synaptophysin or chromogranin A), molecular features (TP53, PTEN, and/ or RB1 loss), serum markers (chromogranin A or neuron-specific enolase), or clinical factors (progression of visceral metastases in the absence of PSA progression). Patients must have a positive Ga-68 DOTATATE PET/CT to proceed with Lu-177 DOTATATE therapy, defined as at least 1 lesion with a maximum standardized uptake value (SUV max ) greater than the mean SUV of normal liver. The primary objective for the trial is objective response rate (ORR), defined by Prostate Cancer Working Group 3 (PCWG3) criteria. Secondary objectives include 6-month radiographic progression-free survival as well as the correlation between ORR and change in fluorodeoxyglucose PET/CT signal pre- to mid-treatment. Exploratory objectives include SPECT/CT-based dosimetry of Lu-177 DOTATATE and gene expression analysis of circulating tumor cells collected prior to treatment, during treatment, and at time of progression. A pre-specified activity goal for the first 15 enrolled patients was met, and accrual of an additional 10 patients is currently in progress. Clinical trial information: NCT05691465 .