Pembrolizumab Hits Nearly 90% Response Rate in Desmoplastic Melanoma

Pembrolizumab (Keytruda) elicited a clinical response in nearly 90% of patients with unresectable desmoplastic melanoma, according to findings from a phase 2 trial published in Nature Medicine.^1,2

The objective response rate among 27 evaluated patients was 89% (95% CI, 71%-98%), including a complete response rate of 37% (95% CI, 19%-58%). The 3-year melanoma-specific progression-free survival (PFS) rate was 84% and the 3-year overall survival (OS) rate was 96%. There was 1 patient death due to progressive disease.

The researchers reported that responses were frequently rapid and durable. Tumor reduction for some patients was observed within 2 months of initiating pembrolizumab. Eighty-four percent of patients were alive after 3 years, with nearly three-fourths of patient showing no indications of tumor progression.

Grade 3/4 adverse events (AEs) occurred in 10 patients (37%). AE-related treatment discontinuation was reported in 9 patients (33%). The researchers attributed these discontinuations primarily to the older age and other health conditions of the patient population.¹

“The promising results from this trial show that pembrolizumab can offer durable benefit for patients with a melanoma subtype that previously had no successful treatment options, and now we know that desmoplastic melanoma is among the cancers with the highest response rates to the anti–PD-1 class of cancer immunotherapies,” Antoni Ribas, MD, PhD, the study’s senior author and a professor of medicine at the David Geffen School of Medicine at UCLA and director of the UCLA Health Jonsson Comprehensive Cancer Center’s Tumor Immunology Program, stated in a press release.

“This advances our understanding of exceptional responders to cancer immunotherapy, and it changes the treatment paradigm with a highly active and low toxicity treatment approach,” added Ribas.

Study Design and Background

Desmoplastic melanoma, a rare histologic subtype of melanoma, is amelanotic and presents as a firm nodule or plaque, making it challenging to diagnose and often resulting in an initial misdiagnosis as a benign lesion.³

Overall, the SWOG S1512 study (NCT02775851) evaluated pembrolizumab in patients with desmoplastic melanoma that was either resectable (cohort A) or unresectable (cohort B). The data published in Nature Medicine were from cohort B and comprised 27 patients with unresectable desmoplastic melanoma.

Enrollment criteria for cohort B included histologically or cytologically confirmed primary desmoplastic melanoma that is unresectable; no prior systemic treatment for this melanoma; and no radiation therapy, non-cytotoxic agents, investigational agents, or systemic corticosteroids within 2 weeks before registering for the trial. Patients were excluded from enrollment if they had brain metastases unless the metastases were asymptomatic after treatment and there was no lasting neurological dysfunction.⁴

All patients received 200 mg of pembrolizumab intravenously every 3 weeks for a maximum of 2 years. Complete response rate was the primary end point and secondary end points included melanoma-specific PFS and OS.

“Patients with advanced desmoplastic melanoma demonstrate a high response rate to single-agent PD-1 blockade therapy, reinforcing the use of anti–PD-1 as the preferred treatment option for this disease,” Ribas, who is also director of the Parker Institute for Cancer Immunotherapy Center at UCLA and member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, stated in the press release. “It offers a less invasive, more targeted approach compared to surgery, radiation or combination immunotherapies, which can have more severe side effects.”

The research was supported by grants from SWOG, the National Institutes of Health, and the National Cancer Institute.

REFERENCES:

1. Heady D. Immunotherapy helps extend the lives of patients with rare form of skin cancer, new study finds. UCLA Health Newsroom. Published August 14, 2025. Accessed August 14, 2025. https://tinyurl.com/5bnexret

2. Kendra, K.L., Bellasea, S.L., Eroglu, Z. et al. Anti-PD-1 therapy in unresectable desmoplastic melanoma: the phase 2 SWOG S1512 trial [published online August 14, 2025. Nat Med (2025). https://doi.org/10.1038/s41591-025-03875-5

3. Kendra KL, Contreras CM, Verschraegen CF, Wu RC, Hasanov M. Management of cutaneous melanoma, with a special focus on desmoplastic Melanoma. Am Soc Clin Oncol Educ Book. 2025;45(3):e472752. doi:10.1200/EDBK-25-472752

4. Pembrolizumab in Treating Patients With Desmoplastic Melanoma That Can or Cannot Be Removed by Surgery(NCT02775851). ClinicalTrials.gov. Last updated August 13, 2025. Accessed August 15, 2025. https://clinicaltrials.gov/study/NCT02775851