This randomized phase 2 Neo Trio trial investigated whether adding targeted therapy (dabrafenib plus trametinib) to neoadjuvant immunotherapy (pembrolizumab) improves long-term recurrence-free survival in patients with resectable stage III BRAFV600-mutant melanoma. Sixty patients were randomized to pembrolizumab alone, sequential therapy (dabrafenib/trametinib followed by pembrolizumab), or concurrent triple therapy. The primary outcome was pathological response; secondary outcomes included radiographic response, recurrence-free survival, overall survival, and safety. All three treatment arms met the primary endpoint, with concurrent therapy showing the highest pathological response rate (80%). However, recurrences after major pathological response were more common in the targeted therapy arms. The study suggests that combining targeted therapy with neoadjuvant immunotherapy may not be beneficial and may reduce the quality of the response, thus the combination is not recommended pending longer follow-up.

Georgina V. Long, Matteo S. Carlino, George Au-Yeung, Andrew J. Spillane, Kerwin F. Shannon, David E. Gyorki, Edward Hsiao, Rony Kapoor, Jake R. Thompson, Iris Batula, Julie Howles, Sydney Ch’ng, Maria Gonzalez, Robyn P. M. Saw, Thomas E. Pennington, Serigne N. Lo, Richard A. Scolyer, Alexander M. Menzies