FDA Grants Breakthrough Device Designation to Merlin CP-GEP in Early-Stage Melanoma

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.¹ The designation is intended to expedite development and regulatory review of technologies that may improve diagnosis or management of life-threatening disease.

According to the press release, Merlin CP-GEP is now the only commercially available melanoma GEP test to hold both FDA breakthrough device status and inclusion in the NCCN Clinical Practice Guidelines in Oncology for cutaneous melanoma.² Additionally, results from the observational MERLIN_001 trial (NCT04759781) helped support this FDA decision.³

“Breakthrough device designation underscores the potential of Merlin CP-GEP to advance personalized melanoma care and support more informed, patient-centered treatment decisions,” Dharminder Chahal, chief executive officer of SkylineDx, said in the press release.¹ “Patients deserve access to the best available tools supported by rigorous clinical evidence and recognized in clinical practice guidelines.”

NCCN Guideline Update

The FDA action builds on a recent update to the NCCN cutaneous melanoma guidelines, which now references CP-GEP testing as an option to support shared decision-making about sentinel lymph node biopsy (SLNB) in patients with T1b and T2a tumors, a population in which nodal metastatic risk often falls into an intermediate, clinically ambiguous range.³ The updated language specifies that CP-GEP may be considered in select patients with T1b and T2a cutaneous melanoma when a patient or clinician would elect to forgo SLNB if the true risk of nodal involvement were below 10%.

MERLIN_001: The Evidence Base

The MERLIN_001 trial is described as the largest prospective, multicenter, blinded evaluation of a melanoma GEP-based test to date, and was published in JAMA Surgery.³ Investigators from 9 academic centers enrolled 1761 patients with clinically lymph node-negative, T1 to T3 cutaneous melanoma (Breslow thickness ≤4.0 mm) who underwent SLNB and had a successful CP-GEP assay performed on formalin-fixed, paraffin-embedded biopsy tissue. The test succeeded in 97.7% of submitted samples.

Overall, 17.6% of patients had a positive sentinel node. CP-GEP classified 37.0% of cases as low risk, among whom the observed sentinel lymph node positivity rate was 7.1%, yielding a negative predictive value (NPV) of 92.9% (95% CI, 90.7%-94.8%). High-risk cases had a 23.8% sentinel node metastasis rate (95% CI, 21.3%-26.4%), roughly 3-fold higher than low-risk cases. Because the trial’s prespecified success threshold required an upper 95% CI bound below 5% for low-risk cases, the study’s primary objective was not met at the full-cohort level.

Performance varied notably by substage. Low-risk classification was common in T1 tumors (68.2%) but rare in T2b (17.4%) and nearly absent in T3 (2.8%), limiting the test’s practical utility in higher-stage disease. In the clinical stage IB subgroup (T1b/T2a), which comprised 67.4% of the cohort—the population now referenced in the NCCN update—49.3% of cases were low risk, with a 6.5% observed nodal positivity rate (95% CI, 4.6%-8.8%) vs 18.3% (95% CI, 15.3%-21.6%) in high-risk cases.

Similar patterns held among patients 65 years and older, in whom low-risk cases had a 6.6% (95% CI, 4.2%-9.7%) positivity rate vs 20.3% (95% CI, 16.8%-24.2%) for high-risk cases. Investigators noted that because the observed risk in low-risk stage IB and older-adult subgroups remained within the 5%-to-10% range, results support the test as an adjunct for discussion rather than a basis for unilaterally forgoing SLNB in all patients.

References

1. SkylineDx's Merlin CP-GEP granted FDA breakthrough device designation, building on exclusive NCCN recognition in melanoma care. News release. July 1, 2206. Accessed July 1, 2026. https://tinyurl.com/553pf3me
2. NCCN Clinical Practice Guidelines. Melanoma: Cutaneous, version 2.2026. Updated April 17, 2026. Accessed July 1, 2026. https://tinyurl.com/3z8xk7h
3. 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