2026-09-19
9 academic centers
Clinically node-negative T1–T3 melanoma
Primary biopsy tissue
CP-GEP → low risk or high risk
Standard SLNB
Performed for all patients
CP-GEP result
Compared with observed SLN status
Clinically node-negative T1–T3 melanoma; pT1a permitted only with selected high-risk features.
8-gene expression signature + Breslow thickness + age → low-risk or high-risk result.
Could a low-risk result define a group that could safely forgo SLNB? Prespecified bar: upper 95% CI <5%.
Identify a CP-GEP “low-risk” group with an actual SLN positivity rate
Low-risk SLN positivity was 7.1%, above the <5% threshold used to define a “no-SLNB” group.
A low-risk result placed the group at 7.1% SLN positivity — squarely in the guideline 5–10% discussion / consideration zone.
A low-risk CP-GEP result places many patients into the range where guidelines support discussion and consideration of SLNB rather than an automatic recommendation.
Low-risk CP-GEP did not reach the prespecified <5% SLN-positivity threshold.
Initial framing: “failed primary endpoint.”High-risk results carried a 3.4-fold higher risk of SLN metastasis; low-risk patients clustered below 10%.
Interpretation shifts from omission to risk refinement.NCCN language recognizes CP-GEP for selected patients to support shared decision-making around SLNB.
Use selectively — not as a blanket no-SLNB rule.Biopsy proves melanoma
Dermatology or surgery recognizes an SLNB-eligible patient
Existing biopsy tissue used; no new procedure
Result returns before SLNB is finalized
Result incorporated into the SLNB conversation
A decade ago, this degree of long-term survival was not the expected natural history of metastatic melanoma.
10-year melanoma-specific survival among patients alive and progression-free at 3 years on nivo + ipi
were not alive at 10 years
Durable benefit is real.Vusolimogene oderparepvec-wtpg is indicated in combination with nivolumab for adults with unresectable advanced cutaneous melanoma who experienced disease progression on a PD-1–blocking antibody–based regimen.
Intratumoral RP1 starts where the lesion can be reached.
Local tumor destruction may broaden antigen exposure.
The goal is a systemic antitumor response.
Systemic therapy continues while injected lesions provide local immune stimulation.
RP1 intratumorally every 2 weeks for up to 8 doses; nivolumab started with the second RP1 dose.
Use this as trial-regimen language unless final label details are being quoted directly.This is not “just another systemic drug”: lesion selection, injection logistics, and the distinction between injected and noninjected disease are central to the therapy.
PD-1–refractory advanced melanoma
Reliability / interpretability of efficacy data
Public discussion and vote
Based on ORR + DOR
Verify clinical benefit
Accelerated approval means the response signal was judged sufficient to allow access now — while longer-term clinical benefit still has to be verified.
For an update talk, the debate is not a distraction. It is the lesson: accelerated approval is a regulatory pathway for promising but incomplete evidence.
MERLIN_001 strengthens the evidence that CP-GEP can refine SLN risk — but predictive performance is not yet the same thing as proven benefit from changing management.
CheckMate 067 shows that advanced melanoma can have decade-long survival. The first few years matter enormously — but a large unmet need remains.
RP1 + nivolumab is now FDA-approved after PD-1 progression. Tumor accessibility and noninjected disease are part of the treatment conversation.