Merlin CP-GEP Receives Breakthrough Device Designation to Assess Need for Melanoma SLNB

The FDA has granted breakthrough device designation (BDD) to Merlin CP-GEP, a clinicopathologic gene expression profile (CP-GEP) test designed to support risk assessment and clinical decision-making in patients with early-stage cutaneous melanoma, SkylineDx announced in a news release.¹ The designation makes Merlin CP-GEP the first and only melanoma gene expression profiling test to hold both FDA BDD and inclusion in NCCN Clinical Practice Guidelines in Oncology for cutaneous melanoma.

The BDD program is designed to expedite development and review of novel technologies that may provide more effective diagnosis or management of life-threatening or irreversibly debilitating diseases. The designation was supported by data from the MERLIN_001 trial (NCT04759781), which SkylineDx describes as the largest prospective multicenter blinded clinical trial in cutaneous melanoma.

Clinical Context and NCCN Recognition

The NCCN has incorporated Merlin CP-GEP into its Version 1.2026 cutaneous melanoma guidelines as potentially appropriate for sentinel lymph node biopsy (SLNB) risk stratification in some patients.² This can help patients avoid an unnecessary procedure if they are not at high risk.

The NCCN guidelines state that CP-GEP testing may be used in select patients with T1b and T2a melanoma to support shared decision-making when a patient or provider would decide against SLNB if the true risk were below 10%. The NCCN guidelines distinguish Merlin CP-GEP from other commercially available GEP assays, specifying that alternative GEP tests for SLNB risk prediction are not recommended outside of clinical trials based on currently available evidence.

Patients with stage IB (T1b/T2a) cutaneous melanoma represents a clinically important group in which absolute nodal metastasis risk is often intermediate and the decision to pursue SLNB can be nuanced. SLNB remains a key staging procedure in clinically node-negative melanoma and provides prognostic information relevant to adjuvant therapy discussions, but carries procedural risks including seroma, infection, and lymphedema, without conferring a melanoma-specific survival advantage in all subgroups. Accurate risk stratification in this intermediate-risk population has therefore been a sustained area of clinical interest.

MERLIN_001 Trial Data

The BDD was informed by prospective data from MERLIN_001, published in JAMA Surgery in 2025.³ In 1761 patients who received CP-GEP testing and underwent SLNB, 651 were classified as low risk. SLN positivity was 7.1% in the low-risk group vs 23.8% in the high-risk group, reflecting approximately a threefold higher likelihood of SLN positivity in patients classified as high risk. In patients with low-risk stage IB disease specifically, SLN positivity was 6.5% vs 18.3% in the high-risk group. Among patients aged 65 or older, SLN positivity was 6.6% in those classified as low risk versus 20.3% in those classified as high risk.

The study was designed to address limitations of earlier retrospective GEP studies through prospective enrollment and blinded outcome assessment. However, MERLIN_001 evaluated predictive performance for SLN status rather than downstream clinical utility and was not designed to test whether CP-GEP–guided decision-making improves patient-centered outcomes such as survival or quality of life.

Assay Design and Availability

Merlin CP-GEP is the only commercially available GEP test that integrates clinicopathologic variables, including patient age and Breslow thickness, with the expression of 8 melanoma-associated genes into a single integrated algorithm generating a binary high- or low-risk output for metastasis.¹ The model was developed through a collaboration between investigators at the Mayo Clinic and SkylineDx. The test is available in the United States as a laboratory-developed test and is marketed in the European Union, European Economic Area, and United Kingdom as the Merlin Assay, a CE-IVD and UKCA-marked device.

“[BDD] underscores the potential of Merlin CP-GEP to advance personalized melanoma care and support more informed, patient-centered treatment decisions,” Dharminder Chahal, MSc, chief executive officer of SkylineDx, stated in the news release.

REFERENCES

1. SkylineDx's Merlin CP-GEP Granted FDA Breakthrough Device Designation, Building on Exclusive NCCN Recognition in Melanoma Care. News release. SkylineDx. July 1, 2026. Accessed July 1, 2026. https://tinyurl.com/ystxxnzu

2. 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

3. NCCN. Clinical Practice Guidelines in Oncology. Cutaneous melanoma, version 1.2026. Accessed July 1, 2026. https://tinyurl.com/5b39f96p