According to results from a multicenter, phase 2 trial, neoadjuvant pembrolizumab demonstrated both efficacy and safety among patients with stage IIB/IIC melanoma without risking increased sentinel lymph node (SLN) metastasis. 

These data were first presented by Giorgos Constantine Karakousis, MD, University of Pennsylvania, Philadelphia, Pennsylvania, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

In this single-arm study, researchers enrolled 63 treatment-naive patients to receive 200 mg of pembrolizumab prior to wide excision and SLN biopsy followed by pembrolizumab once every 3 weeks for up to 1 year or until disease progression or unacceptable toxicity. The primary end point was SLN positivity rate. Key secondary end points included recurrence-free survival (RFS) and safety.  

At analysis, the SLN positivity rate was 27%. After a single dose of pembrolizumab 28 patients had residual primary tumor and 4 patients were upstaged from stage IIB to stage IIC. There was an 18% reduction in SLN positivity compared to historical control (P = .302) and in a subgroup of patients with stage IIC disease, SLN metastasis rate was 16.7% compared to 40% (P = .009) based on initial biopsy and 23.5% compared to 40% (P = .0499) based on primary tumor staging at wide excision. The 2-year RFS rate was 84% with a median time to recurrence of 9.9 months. Grade 3/4 treatment-related adverse events occurred in 22% of patients with 9 immune-related adverse events. Treatment-related adverse events did not lead to surgical delay. 

“Neoadjuvant therapy in clinical stage IIB/C was safe and feasible, with no significant delay in surgery or new or unexpected toxicities… [and SLN metastasis rate] did not differ significantly compared to expected historical rates,” concluded Dr Karakousis et al. “Translational studies are under way, including flow cytometric and transcriptional studies, that may reveal immunologic determinants of efficacy versus resistance.”

Source: 

Miura J, Farooq M, Gimotty P, et al. Neoadjuvant-adjuvant pembrolizumab in clinical stage IIB/C melanoma. Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 9502