Tellbio’s Technology Demonstrates Analysis of Circulating Tumor Cells Can Predict Survival Among Patients With Metastatic Castration-Resistant Prostate Cancer Receiving Radium-223

TellBio, Inc. recently announced publication of data that shows the promise of CTCs as a prognostic biomarker for patients with prostate cancer receiving novel therapies such as radium-223. The paper, Circulating and Imaging Biomarkers of Radium-223 Response in Metastatic Castration-Resistant Prostate Cancer, was published in JCO Precision Oncology (DOI 10.1200/PO.23.00230).

“Radium-223 is a valuable treatment option for patients with mCRPC, but better biomarkers are needed to identify patients most likely to benefit from therapy. This study suggests that CTC analysis may be a promising candidate for such circulating biomarkers,” said Annie Partisano, PharmD, MS, Senior Vice President and Head of Operations, TellBio, Inc.

Radium-223 is FDA-approved for the treatment of castrate-resistant prostate cancer (CRPC) with bone metastases and no known visceral proliferation. While radium-223 has improved overall survival (OS), delayed first symptomatic skeletal events, and improved quality of life (QoL), there are currently no prognostic and predictive biomarkers to guide the use of this therapy. Additionally, imaging assessment in patients with bone-predominant disease has also been limited in patients receiving radium-223.

This is the first study to evaluate molecular RNA signatures with CTCs isolated via the TellDx CTC System as a potential biomarker of prognosis in patients receiving radium-223. Within this single-arm, prospective biomarker-driven study, CTC analyses were performed at baseline, 1-month, and 2-months. Isolation of CTCs with the TellDx CTC System and subsequent gene expression with RNA-based digital droplet polymerase chain reaction assay was used to quantify a composite digital CTC_M score. CTC expression of the androgen receptor (AR) slice variant, AR-V7 was also assessed.

The presence of AR-V7 in CTCs has been associated with resistance to AR-targeted therapies, but its relevance to radium-223 treatment is unknown. The study enrolled 22 adult men with bone metastatic CRPC undergoing radium-223 treatment. Median OS was 36.6 months for patients with CTC_M <20 versus 15.6 months for CTC_M >20 (p=0.00341; HR, 5.874 [95% CI, 1.582 to 21.81]) and 11.8 months for patients with detectable baseline AR-V7 versus 31.1 months for those without (p=0.00195; HR, 5.198 [95% CI, 1.657 to 16.31]).   There was no significant association between the number of CTCs and the presence of AR-V7. Upon controlling for known prognostic markers, PSA and tAP, the presence of baseline CTC AR-V7 expression was most predictive of OS among patients receiving radium-223.

“These results are encouraging and suggest that circulating biomarkers may be useful in guiding the use of radium-223 therapy,” said David T. Miyamoto, MD, PhD, Assistant Professor of Radiation Oncology at Harvard Medical School and attending radiation oncologist at the Massachusetts General Hospital.

This prospective study was the first to evaluate molecular RNA signatures in microfluidically isolated CTCs as potential biomarkers of prognosis with radium-223. This study provides another means of potentially personalizing treatment in patients with mCRPC.

TellDx ids a development-stage medical technology company focused on revolutionizing the detection of cancer metastasis through its unique and proprietary CTC technology. The TellDx CTC System, a fully functional diagnostic solution, isolates live CTCs from patient liquid biopsies. The platform has been developed and optimized following a decade of research and development. TellDx offers a unique opportunity to isolate CTCs via its microfluidic diagnostic platform to advance translational and clinical efforts and optimize the lives of patients with cancer.