Background
Phase III, N=246, stage IIIB/C melanoma; 74% had ≥2 prior surgical resections, 35% prior systemic therapy.
Interventions and follow up
Arm A: Weekly intralesional daromun (13 MIU L19IL2 + 400 mcg L19TNF) for 4 weeks then surgery
Arm B: Upfront surgery
Primary endpoint: Recurrence-free survival (RFS)
mFollow up: Median 21 month
Arm B: Upfront surgery
Primary endpoint: Recurrence-free survival (RFS)
mFollow up: Median 21 month
Results
RFS: Median 16.7 vs 6.8 months, HR 0.59 (95% CI 0.41–0.86), P=.005
Distant recurrence: HR 0.60 (95% CI 0.37–0.95), P=.029 (40% reduction)
Distant recurrence: HR 0.60 (95% CI 0.37–0.95), P=.029 (40% reduction)
Adverse events
Main adverse events: Grade ≥3 TRAEs: 27.1% daromun vs 6.7% surgery alone; mostly injection-site reactions, transient and manageable
Conclusions
Neoadjuvant daromun significantly improves RFS vs upfront surgery in stage III melanoma. Offers new option for locoregional recurrence after prior surgery and adjuvant therapy.
Key Limitations
Key Limitations: Single-arm comparison to surgery alone; prior systemic therapy allowed; primarily European population; follow-up still maturing at 21 months.
Clinical Context
First intralesional immunocytokine regimen showing RFS benefit in stage III melanoma. Potential practice-changing for locally advanced, surgically resectable disease with recurrence history. Complements existing checkpoint inhibitor adjuvant approaches.
References
References: Kähler et al, Ann Oncol 2025