The FDA has granted breakthrough device designation to Merlin CP-GEP, a clinicopathologic gene expression profile (CP-GEP) test intended to support risk assessment and clinical decision-making in patients with early-stage cutaneous melanoma. The designation makes Merlin CP-GEP the first and only melanoma gene expression profiling test to hold both FDA breakthrough device designation and inclusion in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology.¹
The designation was supported in part by data from the MERLIN_001 study (NCT04759781), described by the developer as the largest prospective, multicenter, blinded clinical trial conducted in cutaneous melanoma to date.² The trial evaluated the test's performance in predicting sentinel lymph node (SLN) status in patients with stage IB (T1b/T2a) disease, a population in which accurate SLN metastatic risk stratification is considered clinically significant given current variability in patient selection for SLN biopsy.
Merlin CP-GEP: Breakthrough Status for a Melanoma Risk Tool
- The FDA granted breakthrough device designation to Merlin CP-GEP, a clinicopathologic gene expression profiling test for early-stage cutaneous melanoma, based in part on prospective data from the MERLIN_001 study published in JAMA Surgery.
- Merlin CP-GEP is the first and only melanoma GEP test to hold both FDA breakthrough device designation and NCCN guideline inclusion, specifically for T1b and T2a cutaneous melanoma.
- The test is currently marketed in the United States as a laboratory-developed test and has not yet received formal FDA market authorization; the breakthrough device designation is intended to expedite that review process.
How was Merlin CP-GEP developed and validated?
Merlin CP-GEP was developed collaboratively by Mayo Clinic and SkylineDx.¹ The test integrates traditional clinicopathologic variables with a gene expression profiling algorithm into a single model. The test provides a binary risk output, classifying patients as high risk or low risk for metastasis, with the intention of mapping directly to surgical action categories described in evidence-based guidelines.
The MERLIN_001 study served as the pivotal prospective clinical validation for the test.² The trial was conducted across multiple centers in a blinded fashion, and its published findings in JAMA Surgery support the test's performance characteristics in the T1b/T2a cutaneous melanoma population.²
The study was conducted from September 2021 to June 2024 at 9 academic medical centers. To be included, patients had to have biopsy-proven invasive cutaneous melanoma with T1 to T3 tumors and clinically negative regional lymph nodes. All patients were eligible for SLN biopsy. GEP was performed on formalin-fixed, paraffin-embedded tissue from the primary melanoma biopsy. The primary end point was negative predictive value (NPV) in low-risk cases.
A total of 1761 patients were included. The median age was 64 years (IQR, 53-72) and most patients were male (n = 997; 56.6%). Of those who underwent SLN biopsy 310 (17.6%) were SLN positive and had a successful CP-GEP test; GEP was successful in 97.7% of samples.
The results indicated that 651 patients (37.0%) were low risk by CP-GEP. Of these cases, 46 (7.1%) were SLN positive, and the NPV was 92.9% (95% CI, 90.7%-94.8%). The SLN-positive rate was 23.8% (n = 264 of 1110) in high-risk cases. Notably, a lower percentage of cases with low-risk CP-GEP were seen with increasing T category (T1: n = 346 of 507; 68.2%; T2: n = 295 of 897; 32.9%; T3: n = 10 of 357; 2.8%).
CP-GEP results were consistent in differentiating SLN-positive rates across primary sites, histologic subtypes, and mitotic count categories. A total of 6.5% (95% CI, 4.6%-8.8%) of low-risk clinical stage IB cases were SLN positive vs 18.3% (95% CI, 15.3%-21.6%) of high-risk cases. Additionally, 6.6% (95% CI, 4.2%-9.7%) of low-risk cases in patients 65 years and older were SLN positive vs 20.3% (95% CI, 16.8%-24.2%) of high-risk cases.
What is the current NCCN guideline status?
Merlin CP-GEP is currently included in the NCCN Clinical Practice Guidelines in Oncology for Cutaneous Melanoma as a predictive GEP test that may be used to support metastatic risk assessment and clinical decision-making in T1b and T2a melanoma.³ This recognition preceded the FDA designation and provides a guideline-supported framework for incorporating the test into management discussions for this early-stage population.
According to the NCCN guidelines, appropriate use of the test in this context includes support for patient selection for SLN biopsy, informing follow-up strategies, and facilitating shared decision-making.³
References
- SkylineDx's Merlin CP-GEP granted FDA breakthrough device designation, building on exclusive NCCN recognition in melanoma care. News release. PR Newswire. July 1, 2026. Accessed July 1, 2026. https://www.prnewswire.com/news-releases/skylinedxs-merlin-cp-gep-granted-fda-breakthrough-device-designation-building-on-exclusive-nccn-recognition-in-melanoma-care-302813429.html
- Hieken TJ, Egger ME, Angeles CV, et al. Gene expression profile–based test to predict melanoma sentinel node status: the MERLIN_001 study. JAMA Surg. 2025;160(12):1358-1366. doi:10.1001/jamasurg.2025.4399
- NCCN. Clinical Practice Guidelines in Oncology. Melanoma: cutaneous, Version 2.2026. Accessed July 1, 2026. https://www.nccn.org/guidelines/guidelines-detail?id=1492
