NEOADJUVANT PEMBROLIZUMAB achieved a 71% pathological complete response rate in patients with resectable desmoplastic melanoma, meeting the prespecified primary endpoint in the phase 2 SWOG S1512 trial.
Neoadjuvant Pembrolizumab in Resectable Desmoplastic Melanoma
The phase 2 SWOG S1512 trial was designed to evaluate response to pembrolizumab, an anti-programmed cell death protein 1 therapy, in individuals with desmoplastic melanoma. Findings from cohort A focused on the pathological complete response following neoadjuvant pembrolizumab in patients with surgically resectable disease.
Twenty-eight eligible patients with resectable desmoplastic melanoma received intravenous pembrolizumab at a dose of 200 mg every 3 weeks for three cycles prior to surgical excision. Tissue samples were reviewed at baseline, at 3–5 weeks after treatment initiation, and again at the time of surgery. Secondary endpoints included clinical response rate, overall survival, and treatment related toxicities.
Pathological Complete Response And Clinical Outcomes
The primary endpoint was the pathological complete response rate by local pathological review. Data were as follows: 71%; 95% CI: 51–87; P<0.001. This met the prespecified endpoint, indicating a substantial tumour response to neoadjuvant pembrolizumab in this population.
In addition to pathological complete response, investigators assessed clinical response rate and overall survival. Follow up extended to three years, enabling preliminary evaluation of longer-term outcomes in this cohort of patients with resectable desmoplastic melanoma.
Survival And Safety Findings
At three years of follow up, four participants had died. None of the deaths were known to be attributable to melanoma or to treatment related adverse events. These findings provide important context regarding longer term outcomes following neoadjuvant pembrolizumab in this setting.
Treatment was generally well tolerated. Two patients experienced grade 3 treatment related adverse events, representing 7% of the study population. No additional high-grade toxicities were reported in the abstract.
Overall, neoadjuvant pembrolizumab in patients with resectable desmoplastic melanoma resulted in a high pathological complete response rate alongside an acceptable safety profile. The data were supportive of further evaluation of neoadjuvant programmed cell death protein 1 blockade in this distinct melanoma subtype.
Reference
Kendra KL et al. Neoadjuvant PD-1 blockade in surgically resectable desmoplastic melanoma: cohort A of the phase 2 SWOG S1512 trial. Nat Cancer. 2026;https://doi.org/10.1038/s43018-025-01113-y.
