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 for patients with early-stage cutaneous melanoma. The designation makes Merlin CP-GEP the first and only melanoma gene expression profiling test to hold FDA breakthrough device designation and be included in the NCCN Clinical Practice Guidelines in Oncology.¹
The designation was supported in part by data from the observational 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 both hold FDA breakthrough device designation and be included in NCCN guidelines, specifically for T1b and T2a cutaneous melanoma.
- The test is 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 or low risk for metastasis, with the intention of directly mapping 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 56% of patients were male (n = 997). 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 was 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
