Largest Prospective Study to Date Further Supports Performance of DecisionDx-UM for Metastatic Risk Stratification in Uveal Melanoma and Utility of PRAME Biomarker for Refining Risk When Considered with DecisionDx-UM Class Result

Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, today announced new data from a study further confirming the performance of its DecisionDx-UM test as a robust independent predictor of metastasis-free survival (MFS) in patients diagnosed with UM. Further, the study provides prospective validation data supporting Preferentially Expressed Antigen in Melanoma (PRAME) as a risk refinement tool when considered in the context of a Class 1 or Class 2 DecisionDx-UM test result. The data was presented at the Association for Research in Vision and Ophthalmology (ARVO) 2024 Annual Meeting in Seattle.

Uveal melanoma is an aggressive cancer of the eye, and despite high primary tumor cure rates, metastatic disease spread eventually impacts about half of all patients.¹ The DecisionDx-UM test is considered the standard of care in the management of newly diagnosed UM to assist in determining risk of metastasis, which is critical for informing appropriate treatment plans.

“The latest findings from the COOG2 study not only further support DecisionDx-UM’s ability to predict metastatic risk, but also highlight the utility of PRAME as a valuable adjunct biomarker for further risk refinement when considered in conjunction with a DecisionDx-UM result,” said lead study author and COOG investigator Zelia Correa, M.D., Ph.D., professor of ophthalmology and director of ocular oncology at the Bascom Palmer Eye Institute and Sylvester Comprehensive Cancer Center of the University of Miami Miller School of Medicine. “The study data provides support for combining the reported expression status of the PRAME gene with the DecisionDx-UM class result to enhance metastatic risk prediction. Specifically, distinguishing between PRAME-negative (-) and PRAME-positive (+) subgroups within DecisionDx-UM Class 1 and Class 2 tumors provides additional biological insights into an individual patient’s likelihood of metastasis. This information can be utilized to optimize surveillance and guide more nuanced and risk-aligned treatment decisions.”

Details regarding the presentation at ARVO are included below:

• Oral Presentation Title: Collaborative Ocular Oncology Group study 2 (COOG2): Prospective multi-center validation of the 15-gene expression profile (GEP)/PRAME molecular prognostic tool for uveal melanoma in 1586 patients
• Session Type:Paper Session (Wednesday, May 8)
• Presentation Number: 4273
• Summary: This prospective, multi-center study included 1,586 patients with posterior UM tumors enrolled across 26 ocular oncology centers in the United States and Canada. In the study, a DecisionDx-UM Class 2 result was the most robust independent predictor of MFS (HR 6.03; 95% CI, 4.49-8.09); P<0.001), followed by PRAME status (HR 1.77; 95% CI, 1.39-2.27; P<0.001). Patients with Class 2 tumors had considerably worse outcomes than those with Class 1 tumors, regardless of PRAME status; however, PRAME+ tumors fared worse within each GEP class (versus PRAME-). When considered together, five-year MFS rates were 95.6% (95% CI, 93.9-97.4) for Class 1/PRAME-, 80.6% (73.9-87.9) for Class 1/PRAME+, 57.6% (50.6-65.7) for Class 2/PRAME- and 44.8% (38.0-52.8) for Class 2/PRAME+. Overall, the study confirms the prognostic accuracy of the DecisionDx-UM test and provides the first prospective validation of PRAME status as a risk refinement tool when considered in the context of a Class 1 or Class 2 DecisionDx-UM result. These two tests together can guide more precise and risk-aligned decision-making for patients with UM, including referrals, intensity of imaging surveillance and eligibility for ongoing clinical trials.

J. William Harbour, M.D., ophthalmologist, ocular oncologist, and professor and chair of the department of ophthalmology at UT Southwestern Medical Center, is a leading innovator in the treatment and study of UM and an executive committee member of the COOG. As the original developer of the DecisionDx-UM test, which was licensed to Castle in 2009, Harbour continues to drive important advancements in the treatment of UM and co-authored this study with Correa.