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

Rhea-AI Summary

Castle Biosciences, Inc. released new data confirming the effectiveness of DecisionDx-UM in predicting metastasis-free survival in patients with uveal melanoma. The study also validated the PRAME biomarker as a tool to refine risk assessment when combined with the DecisionDx-UM result. The findings were presented at the ARVO 2024 Annual Meeting. Uveal melanoma is a severe eye cancer, and the DecisionDx-UM test is important for determining metastatic risk and guiding treatment plans.

Positive

• The study further confirmed the accuracy of the DecisionDx-UM test in predicting metastasis-free survival in patients diagnosed with uveal melanoma.

• PRAME was validated as a risk refinement tool when assessed alongside a DecisionDx-UM result, offering more precise risk assessment for UM patients.

• The combination of DecisionDx-UM and PRAME helps optimize surveillance, guide treatment decisions, and enhance patient care in uveal melanoma.

Negative

• Despite high primary tumor cure rates, metastatic disease eventually affects about half of all uveal melanoma patients.

• Patients with Class 2 tumors had worse outcomes compared to those with Class 1 tumors, regardless of PRAME status.

• The study highlights the challenges and risks associated with uveal melanoma, even with advanced diagnostic tools like DecisionDx-UM and PRAME.

Insights

Oncology Diagnostics Expert

Castle Biosciences' DecisionDx-UM has received impressive validation in what represents the largest prospective study to date for uveal melanoma risk stratification. The multi-center COOG2 study involving 1,586 patients across 26 centers delivers compelling evidence of the test's prognostic accuracy with a hazard ratio of 6.03 for predicting metastasis-free survival.

What's particularly valuable is the prospective validation of PRAME as a complementary biomarker that refines risk assessment when combined with the DecisionDx-UM class result. The stratification into four distinct risk groups (Class 1/PRAME-, Class 1/PRAME+, Class 2/PRAME-, Class 2/PRAME+) creates a more granular risk assessment framework with 5-year metastasis-free survival rates ranging from 95.6% to 44.8%.

This differentiated risk stratification has meaningful clinical implications. Uveal melanoma's aggressive nature, with eventual metastasis in approximately half of patients despite successful primary tumor treatment, makes accurate risk prediction crucial for clinical management. Physicians can now tailor surveillance intensity and referral patterns based on more precise risk categorization, potentially improving resource allocation in healthcare settings while ensuring high-risk patients receive appropriate monitoring.

The involvement of renowned researchers from Bascom Palmer Eye Institute and UT Southwestern Medical Center lends significant credibility to these findings. For Castle Biosciences, this validation further cements DecisionDx-UM's position as the standard of care in uveal melanoma management and enhances the test's clinical utility through the additional PRAME biomarker integration.

Precision Medicine Analyst

This COOG2 study represents a textbook example of how molecular diagnostics can transform risk stratification in oncology. The statistical significance of DecisionDx-UM as an independent predictor (HR 6.03; 95% CI, 4.49-8.09) demonstrates exceptional prognostic power that clearly outperforms traditional clinical factors in uveal melanoma.

The validation of PRAME as a secondary biomarker creates a sophisticated two-dimensional risk assessment matrix that significantly enhances clinical decision-making. The stark difference between the best-case scenario (Class 1/PRAME- with 95.6% 5-year MFS) and worst-case scenario (Class 2/PRAME+ with 44.8% 5-year MFS) provides actionable stratification that can directly inform clinical management strategies.

From a precision medicine perspective, this approach exemplifies how multi-marker panels can capture tumor biology complexity better than single biomarkers. The original DecisionDx-UM test measures expression of 15 genes, and adding PRAME assessment creates a more comprehensive molecular profile that better reflects the biological heterogeneity of uveal melanoma.

For Castle Biosciences, this validation strengthens their position in the precision oncology diagnostics market. The company's strategy of enhancing existing tests with additional biomarkers like PRAME demonstrates scientific rigor and commitment to continuous improvement of their diagnostic portfolio. This approach of refining risk assessment through layered biomarker analysis represents the future direction of precision diagnostics - not just binary classification but nuanced risk stratification that enables truly personalized medical decisions aligned with individual patient risk profiles.

Oral presentation at ARVO shares ground-breaking findings from the ongoing Collaborative Ocular Oncology Group (COOG) study 2 (COOG2) of patients with uveal melanoma (UM)

FRIENDSWOOD, Texas--(BUSINESS WIRE)-- 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.

The presented abstract described above can be viewed online in the ARVO Meeting Planner.

About DecisionDx®-UM

DecisionDx-UM is Castle Biosciences’ 15-gene expression profile (GEP) test that uses an individual patient’s tumor biology to predict individual risk of metastasis in patients with uveal melanoma (UM). DecisionDx-UM is the standard of care in the management of newly diagnosed UM in the majority of ocular oncology practices in the United States. Since 2009, the American Joint Committee on Cancer (AJCC; v7 and v8) Staging Manual for UM has specifically identified the GEP test as a prognostic factor that is recommended for collection as a part of clinical care. Further, the National Comprehensive Cancer Network (NCCN) guidelines for UM include the DecisionDx-UM test result as a prognostic method for determining risk of metastasis and recommended differential surveillance regimens based on a Class 1A, 1B and 2 result. DecisionDx-UM is currently the only prognostic test for UM that has been validated in prospective, multi-center studies, and it has been shown to be a superior predictor of metastasis compared to other prognostic factors, such as chromosome 3 status, mutational status, AJCC stage and cell type. It is estimated that nearly 8 in 10 patients diagnosed with UM in the United States receive the DecisionDx-UM test as part of their diagnostic workup. More information about the test and disease can be found here.

About DecisionDx®-PRAME

Castle Biosciences offers testing with DecisionDx-PRAME as an optional add-on to the DecisionDx-UM test. PRAME (preferentially expressed antigen in melanoma) is an antigen gene that is not expressed at appreciable levels in normal adult tissues, but its expression can become aberrantly increased in some types of cancer, including melanoma. Once expressed, the PRAME protein can be processed and presented on the surface of cells, thereby serving as a potential target for therapeutic intervention. PRAME-directed therapies are being explored in multiple cancer types, including uveal melanoma. More information about DecisionDx-PRAME can be found here.

About the Collaborative Ocular Oncology Group

The Collaborative Ocular Oncology Group (COOG) is the largest collaborative working group in North America comprised of ocular and medical oncologists specialized in the treatment of patients with intraocular cancers, currently focusing on UM. The group is dedicated to a collaborative, evidence-based approach to advancing the care of patients with UM and other eye cancers through precision diagnostic, prognostic and therapeutic breakthroughs. Comprised of more than 25 leading academic and private ocular oncology centers of excellence, the COOG has been continually funded by the National Cancer Institute for over a decade. The COOG has conducted two large multi-center prospective studies of prognostic biomarkers in UM, the first and only such studies ever conducted in this cancer to date, and is planning a major expansion into adjuvant and metastatic clinic trials in patients with UM. More information about the COOG can be found here.

About Castle Biosciences

Castle Biosciences (Nasdaq: CSTL) is a leading diagnostics company improving health through innovative tests that guide patient care. The Company aims to transform disease management by keeping people first: patients, clinicians, employees and investors.

Castle’s current portfolio consists of tests for skin cancers, Barrett’s esophagus, mental health conditions and uveal melanoma. Additionally, the Company has active research and development programs for tests in other diseases with high clinical need, including its test in development to help guide systemic therapy selection for patients with moderate-to-severe atopic dermatitis, psoriasis and related conditions. To learn more, please visit www.CastleBiosciences.com and connect with us on LinkedIn, Facebook, X and Instagram.

DecisionDx-Melanoma, DecisionDx-CMSeq, DecisionDx-SCC, MyPath Melanoma, DiffDx-Melanoma, TissueCypher, IDgenetix, DecisionDx-UM, DecisionDx-PRAME and DecisionDx-UMSeq are trademarks of Castle Biosciences, Inc.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to the “safe harbor” created by those sections. These forward-looking statements include, but are not limited to, statements concerning: (i) the ability of the DecisionDx-UM test to assist in determining risk of metastasis to inform appropriate treatment plans; (ii) the utility of PRAME as a valuable biomarker when considered in conjunction with a DecisionDx-UM test result; and (iii) the ability of the DecisionDx-UM test and PRAME to guide more nuanced and risk-aligned treatment decisions for patients with UM, including referrals, intensity of imaging surveillance and eligibility for ongoing clinical trials. The words “can,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. These forward-looking statements involve risks and uncertainties that could cause our actual results to differ materially from those in the forward-looking statements, including, without limitation: subsequent study or trial results and findings may contradict earlier study or trial results and findings or may not support the results shown in this study, including with respect to the discussion of DecisionDx-UM in this press release; actual application of our DecisionDx-UM test may not provide the aforementioned benefits to patients; and the risks set forth under the heading “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2023, our Quarterly Report on Form 10-Q for the quarter ended March 31, 2024 and in our other filings with the SEC. The forward-looking statements are applicable only as of the date on which they are made, and we do not assume any obligation to update any forward-looking statements, except as may be required by law.

1. Kujala E, Mäkitie T, Kivelä T. Very long-term prognosis of patients with malignant uveal melanoma. Invest Ophthalmol Vis Sci. 2003 Nov 1;44(11):4651.

 

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Investor Contact:

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Media Contact:

Allison Marshall

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Source: Castle Biosciences Inc.

FAQ

What did Castle Biosciences announce in the press release?

Castle Biosciences announced new data confirming the effectiveness of DecisionDx-UM in predicting metastasis-free survival in patients with uveal melanoma, along with the validation of the PRAME biomarker as a risk refinement tool.

What is the significance of the DecisionDx-UM test in managing uveal melanoma?

The DecisionDx-UM test is considered the standard of care in determining the risk of metastasis in newly diagnosed uveal melanoma patients, important for informing treatment plans.

What was presented at the ARVO 2024 Annual Meeting?

New data from the study confirming DecisionDx-UM's effectiveness and the validation of PRAME as a risk refinement tool were presented at the ARVO 2024 Annual Meeting.

Who presented the study findings at the ARVO meeting?

Lead study author and COOG investigator Zelia Correa, M.D., Ph.D., presented the findings at the ARVO 2024 Annual Meeting.

What is uveal melanoma?

Uveal melanoma is an aggressive cancer of the eye that impacts about half of all patients with metastatic disease eventually.

What is the role of PRAME in risk assessment for uveal melanoma?

PRAME serves as a valuable adjunct biomarker for refining risk assessment when combined with a DecisionDx-UM result, providing additional insights into metastatic likelihood.

Who developed the DecisionDx-UM test?

J. William Harbour, M.D., an ophthalmologist and ocular oncologist, developed the DecisionDx-UM test and co-authored the study with Zelia Correa.

What are the implications of combining DecisionDx-UM and PRAME for uveal melanoma patients?

The combined use of DecisionDx-UM and PRAME can optimize surveillance, guide treatment decisions, and enhance patient care for those with uveal melanoma.

Where can the presented abstract be viewed online?

The abstract presented at the ARVO Meeting can be viewed online in the ARVO Meeting Planner.