Related Experiment Video
Updated: Sep 11, 2025
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
Anti-PD-1 therapy in unresectable desmoplastic melanoma: the phase 2 SWOG S1512 trial
Kari L Kendra1, Shay L Bellasea2,3, Zeynep Eroglu4
1Ohio State University Wexner Medical Center, Columbus, OH, USA. kari.kendra@osumc.edu.
Abstract:
Desmoplastic melanoma is a distinct subtype of melanoma known to have preexisting immune infiltrates and high ultraviolet light damage, resulting in a high tumor mutational burden. We hypothesized that this may result in high response rates with single-agent anti-programmed death protein 1 (PD-1) therapy. SWOG S1512 was a two-cohort clinical trial testing the activity of pembrolizumab in patients with surgically resectable (cohort A) and unresectable (cohort B) desmoplastic melanoma. Here we report on the cohort B single-arm clinical trial, which enrolled 27 patients with unresectable desmoplastic melanoma receiving pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years, with the primary endpoint of complete response rate. The complete response rate was 37% (95% confidence interval: 19-58%), and the post hoc endpoint of objective response rate was 89% (95% confidence interval: 71-98%). The estimated secondary endpoints of 3-year melanoma-specific progression-free survival and overall survival were 84% and 96%, respectively, with only one patient having died from melanoma progression. Ten patients (37%) experienced grade 3 or 4 adverse events, and nine patients (33%) discontinued treatment because of adverse events. Patients with advanced desmoplastic melanoma have a high response rate to single-agent PD-1 blockade therapy, supporting single-agent anti-PD-1 as the treatment of choice, but are limited by a frequency of toxicities that is numerically higher than in other patient populations. ClinicalTrials.gov identifier: NCT02775851.
Insights
Single-agent anti-programmed death protein 1 (PD-1) therapy shows high response rates in patients with unresectable desmoplastic melanoma. Pembrolizumab demonstrated significant efficacy but was associated with notable toxicities.
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- Desmoplastic melanoma is a rare subtype characterized by immune infiltrates and high UV damage.
- This subtype exhibits a high tumor mutational burden, suggesting potential sensitivity to immunotherapy.
- Previous research hypothesized high response rates to anti-programmed death protein 1 (PD-1) therapy.
Purpose of the Study:
- To evaluate the efficacy and safety of single-agent pembrolizumab in patients with unresectable desmoplastic melanoma.
- To determine the complete response rate as the primary endpoint.
- To assess secondary endpoints including objective response rate, progression-free survival, and overall survival.
Main Methods:
- A single-arm clinical trial (SWOG S1512, cohort B) enrolled 27 patients with unresectable desmoplastic melanoma.
- Patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years.
- Primary endpoint was complete response rate; secondary endpoints included objective response rate and survival rates.
Main Results:
- The complete response rate was 37% (95% CI: 19-58%).
- The objective response rate was 89% (95% CI: 71-98%).
- Estimated 3-year melanoma-specific progression-free survival and overall survival were 84% and 96%, respectively. Ten patients (37%) experienced grade 3 or 4 adverse events.
Conclusions:
- Single-agent anti-PD-1 therapy, specifically pembrolizumab, demonstrates high response rates in advanced desmoplastic melanoma.
- This supports anti-PD-1 therapy as a potential treatment of choice for this patient population.
- However, the frequency of toxicities observed was numerically higher than in other patient groups, warranting careful consideration.
