Phase II study of autologous mRNA electroporated dendritic cells (TriMixDC-MEL) in combination with Ipilimumab in patients with pretreated advanced melanoma

Abstract

Background: Autologous monocyte-derived mRNA electroporated dendritic cells (TriMixDC-MEL) are immunogenic and have anti-tumor activity in patients (pts) with pretreated advanced melanoma (Wilgenhof S. et al. Ann Oncol 2013). Ipilimumab (ipi) is a monoclonal antibody directed against the CTLA-4 receptor that counteracts physiologic suppression of T-cell activation and improves the overall survival of pts with advanced melanoma. Methods: The activity and safety of TriMixDC-MEL (4.106 cells id and 20.106 iv, q3wks x4) combined with ipi (10 mg/kg q3wks x4), followed by ipi maintenance therapy (10 mg/kg q12w, in pts who are progression-free at week 24) was investigated in pts with advanced pretreated melanoma according to a Simon two-stage phase II study design. The primary endpoint was the 6-mths disease control rate (DCR) by irRC. Results: 39 pts initiated study treatment (16F/23M; median age 46y [range 24-70]; AJCC stage IIIc/IV M1a/-M1b/-M1c: 1/6/4/28; prior therapy: BRAF- or MEK-inhibitor: 23 pts, chemotherapy: 18 pts). Following DC-administration, gr2 skin injection site reactions were observed in all pts, post-infusion chills (< gr2) in 15 (38%), and transient flu-like symptoms