Abstract PR006: High melanoma-specific survival in patients with desmoplastic melanoma treated with single agent anti-PD-1 in SWOG S1512

Abstract Desmoplastic melanoma is a rare subtype of cutaneous melanoma defined by extensive fibrosis (desmoplasia), and at the same time has pre-existing immune infiltrates and a high tumor mutational burden (TMB) resulting from exposure to ultraviolet (UV) light, which we hypothesized may result in high response rates to single-agent anti-programmed death protein 1 (PD-1) therapy. SWOG S1512 was a two-cohort phase 2 clinical trial: i) Cohort A included 28 eligible patients with surgically resectable desmoplastic melanoma who received a median of 3 infusions (range 1- 4) of neoadjuvant pembrolizumab 200 mg every 3 weeks, followed by surgical excision. pCR rate was 57% (95% CI: 37%-76%, p<0.001); none of the patients received adjuvant pembrolizumab (Kendra et al. ASCO 2022). ii) Cohort B included 27 eligible patients with unresectable desmoplastic melanoma who received a median of 15 infusions (range 1- 34) of pembrolizumab, 200 mg IV every 3 weeks. The objective response rate was 89% (95%, CI:71%-98%; Kendra et al. AACR 2023). At 3 years of follow-up, 13 patients have died (4 cohort A, 9 cohort B). Causes of death were: melanoma (1), cardiac (4), infections (2), stroke (1), pulmonary fibrosis (1), kidney failure (1), acute myelogenous leukemia (1), brain bleed related to a fall (1), and unknown (1). The combined 3-year melanoma-specific survival is 96% (n=55, 95%CI 87%-99%). In conclusion, patients with desmoplastic melanoma are exceptional responders to single-agent PD-1 blockade therapy, leading to long-term responses. Funding for this research was provided by NIH/NCI grants: U10CA180888 and U10CA180819 (SWOG); and in part by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USAFigure 1. Melanoma-specific survival in the combined cohorts A and B of S1512 (n = 55) at 3-year follow up. Death from other causes were treated as competing risks using the Fine-Gray model. Citation Format: Kari L kendra, shay l Bellasea, Zeynep Eroglu, Siwen Hu-Lieskovan, Katie M Campbell, William Carson III, David Wada, Jose A Plaza, Jeffery A Sosman, Gino In, Alexandra P Ikeguchi, John Hyngstrom, Andrew Brohl, Bartosz Chmielowski, Nikhil Khushalani, Joseph Markowitz, George Negrea, Samer Kasbari, Gary C Doolittle, Umang Swami, Toni Roberts, Marcus Monroe, Carlo Contreras, Edmidio Medina, Ignacio Baselga-Carretero, Cynthia R Gonzalez, Ivan Perez Garcilazo, Agustin Vega-Crespo, Jia Min Chen, nataly Nasar Al-Deen, Kenneth F Grossman, Vernon Sondak, elad sharon, Sapna P Patel, james moon, Michael C Wu, Antoni Ribas. High melanoma-specific survival in patients with desmoplastic melanoma treated with single agent anti-PD-1 in SWOG S1512 [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr PR006.