Although immune checkpoint Inhibitor (ICI) therapy has revolutionized the treatment of advanced melanoma, a fraction of patients do not show clinical benefit warranting the development of novel therapies. Cancer vaccines targeting neoantigens (neoAgs) derived from tumor-specific mutations have emerged as a novel and promising treatment modality with a strong safety profile. The personalized neoAg vaccine EVX-01 is under evaluation in combination with pembrolizumab in a phase 2 trial in advanced melanoma (NCT05309421). To understand how EVX-01 shapes anti-tumor immune responses, we characterized the vaccine-induced immune responses in 16 patients and treatment-induced changes in the immune landscape of peripheral blood for a subset of patients.