Despite improvements made with checkpoint inhibitor (CPI) therapy, a need for new approaches to improve outcomes for patients with unresectable or metastatic melanoma remains. EVX-01, a personalized neoepitope vaccine, combined with pembrolizumab treatment, holds the potential to fulfill this need. Here we present the rationale and novel design behind the KEYNOTE - D36 trial: an open label, single arm, phase II trial aiming to establish the clinical proof of concept and evaluate the safety of EVX-01 in combination with pembrolizumab in CPI naive patients with unresectable or metastatic melanoma. The primary objective is to evaluate if EVX-01 improves best overall response after initial stable disease or partial response to pembrolizumab treatment, in patients with advanced melanoma. The novel end points ensure a decisive readout which may prove helpful before making major investments in phase III trials with limited phase I data.
Plain language summary Drugs targeting the immune system have improved the outcomes for patients with advanced melanoma. However, a significant proportion of patients do not benefit and there is a need for better therapeutic agents to be used alone or in combination with immune modulating agents. This article summarizes the rationale and design of a new trial with a personalized vaccine (EVX-01) that may improve outcomes for patients with advanced melanoma (unresectable stage III or IV melanoma). The EVX-01 vaccine aims to stimulate the patient's immune system to generate T cells that target specific molecules that can only be found on the surface of the individual patients' cancer cells (i.e. neoepitopes), resulting in cancer cell death. The trial will investigate if the personalized EVX-01 vaccine together with checkpoint inhibitor therapy works better for patients with advanced melanoma, than checkpoint inhibitor therapy alone.