MERLIN_001 Trial Demonstrates Merlin CP-GEP Test Accurately Stratifies Melanoma Patients by Sentinel Node Metastasis Risk

The MERLIN_001 trial, the largest prospective evaluation of a genomic test in cutaneous melanoma, has demonstrated that the Merlin CP-GEP Test accurately stratifies patients by sentinel lymph node metastasis risk, showing a greater than three-fold difference between High-Risk and Low-Risk groups. Published in the October 2025 issue of JAMA Surgery, the study enrolled 1,761 patients across leading U.S. academic cancer centers including Mayo Clinic, University of Michigan, Memorial Sloan Kettering Cancer Center, and Moffitt Cancer Center.

Results showed that patients with a High-Risk result had a 23.8% rate of sentinel node metastasis compared to 7.1% for those with a Low-Risk result. Overall, 37.0% of patients were classified as Low-Risk while 63.0% were High-Risk, with the test achieving a 97.7% success rate across submitted samples. The study provides quantitative guidance for clinicians regarding the clinical utility of Merlin CP-GEP testing in guiding sentinel lymph node biopsy decision-making.

Dr. Vernon Sondak, MERLIN_001 Principal Investigator and chair of the Cutaneous Oncology Department at Moffitt Cancer Center, stated that the study represents a major step forward in personalized melanoma care. The test adds accuracy above current clinical factors alone, even when accounting for factors like mitotic rate and histologic subtype. This knowledge enables patients and surgeons to make better decisions about when sentinel node biopsy should be part of melanoma management.

The test demonstrated particular utility in challenging patient populations. For patients aged 65 and older, where comorbidities are more prevalent, the test identified 57.9% as High-Risk with a 20.3% positive SLNB rate versus 6.6% for Low-Risk cases. In head and neck melanomas, where SLNB can be technically difficult and carry higher morbidity, the test identified High-Risk cases with a 26.7% SLN rate and Low-Risk cases with 4.9% SLN rate, representing a five-fold risk increase between groups.

Across clinical Stage IB melanoma cases, the test classified 49.3% as Low-Risk with a 6.5% positive SLNB rate compared to an 18.3% rate for High-Risk cases. The Merlin CP-GEP Test is the only commercially available gene expression profiling test that combines clinicopathologic variables with gene expression profiling into a single integrated algorithm, providing binary stratification of all patients based on metastasis risk. The advanced CP-GEP model was developed by Mayo Clinic and SkylineDx and has been clinically validated in multiple global studies.

The implications of these findings are significant for melanoma care worldwide. By accurately identifying patients at low risk of sentinel node metastasis, the test could potentially reduce unnecessary surgical procedures and associated complications while ensuring high-risk patients receive appropriate intervention. The complete MERLIN_001 trial results are available at https://doi.org/10.1001/jamasurg.2025.4399. Additional information about the test and its applications can be found at https://www.falconprogram.com and https://www.merlinmelanomatest.com.