A clinical trial has demonstrated a 71% pathological complete response rate in patients with resectable desmoplastic melanoma following treatment with neoadjuvant pembrolizumab, an anti-programmed cell death protein 1 therapy. The findings, from cohort A of the phase 2 SWOG S1512 trial, represent a significant step forward in the treatment of this rare and aggressive form of skin cancer.
The trial involved 28 patients with surgically resectable desmoplastic melanoma who received intravenous pembrolizumab at a dose of 200 mg every three weeks for three cycles before undergoing surgical removal of the tumor. Researchers analyzed tissue samples taken before treatment, during treatment, and after surgery to assess the response to the immunotherapy.
The primary endpoint of the study – pathological complete response – was met with a rate of 71%, with a 95% confidence interval ranging from 51% to 87% (P<. 0.001). This indicates a substantial reduction or elimination of cancer cells in the removed tissue following the neoadjuvant pembrolizumab treatment. Investigators likewise evaluated clinical response rates and overall survival, with follow-up extending to three years to assess longer-term outcomes.
Over the three-year follow-up period, four participants died, but none of the deaths were attributed to melanoma or treatment-related adverse events. The treatment was generally well-tolerated, with two patients, or 7% of the study population, experiencing grade 3 treatment-related adverse events. No other high-grade toxicities were reported in the study abstract.
Desmoplastic melanoma is a rare subtype of melanoma, accounting for a small percentage of all melanoma cases. It’s often more aggressive and has a poorer prognosis than other types of melanoma. The SWOG S1512 trial provides evidence supporting the further investigation of neoadjuvant programmed cell death protein 1 blockade as a potential treatment strategy for this challenging cancer. The research, published in Nature Cancer, is available under DOI: 10.1038/s43018-025-01113-y.
