New results from a clinical trial co-led by UCLA investigators demonstrate how treating desmoplastic melanoma, a rare and aggressive skin cancer, with immunotherapy before surgery can dramatically shrink or even eliminate tumors, sparing patients from more aggressive surgeries and preserving their quality of life.
The multicenter clinical trial, known as SWOG S1512, was conducted by the SWOG Cancer Research Network and funded by the National Cancer Institute. It marks the first study to test neoadjuvant PD-1 blockade in this population and suggests a promising new treatment approach.
“We’re seeing that desmoplastic melanoma, which can be challenging to remove surgically, responds extremely well to immunotherapy,” said Dr. Antoni Ribas, the study’s senior author, 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. “We found that giving pembrolizumab before surgery is a powerful and safe approach that reduces the need for invasive procedures and improves long-term outcomes.”
Desmoplastic melanoma often develops on sun-exposed areas of skin, such as the head and neck, and grows deep into tissues, sometimes along nerves, making surgery challenging and potentially disfiguring. Historically, wide surgical excision followed by radiation has been the standard approach, while advanced disease was considered largely resistant to systemic therapies such as chemotherapy or immunotherapy.
Building on earlier findings from cohort B of SWOG S1512, which showed that pembrolizumab shrank tumors in nearly 90% of patients with advanced, inoperable desmoplastic melanoma, the current study explored whether the therapy could also benefit patients with surgically removable tumors.
In this group of patients, known as cohort A, 28 patients with surgically resectable desmoplastic melanoma received three infusions of pembrolizumab over nine weeks prior to surgery. Researchers collected tissue samples before, during and after therapy to track tumor response.
The team found that the treatment resulted in a high response rate, with 71% of patients receiving pembrolizumab having no detectable cancer at the time of surgery, and side effects were generally mild.
At the three-year follow-up, 95% of patients had not died from the disease, and 74% remained cancer-free.
“Giving pembrolizumab before surgery led to very high rates of tumor clearance, few serious side effects, and excellent three-year survival for patients with this rare and difficult-to-treat cancer,” said Ribas, who is also director of the Parker Institute for Cancer Immunotherapy Center at UCLA and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. “Taken together with our earlier findings in patients with advanced disease, these results represent a true shift in how desmoplastic melanoma is treated, moving away from repeated surgeries and radiation toward a single therapy that offers durable control, improved survival, and better quality of life.”
Reference:
Kendra, K.L., Bellasea, S.L., Eroglu, Z. 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
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