The checkpoint inhibitor ipilimumab has improved survival for a proportion of patients with metastatic melanoma. However, most patients do not benefit from single agent immunotherapy. Patients lacking a spontaneous immune response may benefit from combining checkpoint blockade with a tumor-specific vaccine. UV1 is a therapeutic cancer vaccine consisting of three long synthetic peptides of the enzyme telomerase (hTERT). The UV1 peptides comprise epitopes recognized by T cells from cancer patients experiencing long-term survival following vaccination with a first-generation hTERT vaccine. The aim of this trial was to investigate the safety and efficacy of combining UV1 and ipilimumab in the treatment of patients with metastatic melanoma.
In a phase I, single center trial [EudraCT No. 2013-005582-39], patients with metastatic melanoma received treatment with UV1 (300 µg) + GM-CSF (75 µg) as adjuvant, combined with ipilimumab (3 mg/kg). Safety was assessed according to CTCAE v. 4.0, and tumor responses according to RECIST v.1.1. Immune responses against UV1 peptides were monitored in peripheral mononuclear blood cells by using 3H-thymidine proliferation and IFN-γ ELISPOT assays.
12 patients were recruited from Jan to Oct 2015. Treatment was generally well tolerated. Adverse events mainly included injection site reactions and diarrhea. Eleven serious adverse events (SAEs) were reported; nine treatment-related and two not related. Ten out of twelve patients showed an immune response (one negative, one not evaluable). Three patients obtained a partial response. Overall survival at 18 months was 75%. A comparison to a reference population from a phase IV ipilimumab trial in our center will be made.
Combining UV1 and ipilimumab is safe and induces clinical responses. The high proportion of immune responders and early induction of detectable immune responses suggest a synergistic effect due to de novo tumor-specific immune responses, likely due to blockage of CTLA-4, allowing expansion of hTERT-specific T-cell clones.
Clinical trial identification
EudraCT No. 2013-005582-39 Start date 16 Jan 2015
Legal entity responsible for the study
Ultimovacs AS Ullernschausséen 64 NO-0379 Oslo Norway Ultimovacs AS Ullernschausséen 64 NO-0379 Oslo Norway Ultimovacs AS Ullernschausséen 64 NO-0379 Oslo Norway Ultimovacs AS Ullernschausséen 64 NO-0379 Oslo Norway Ultimovacs AS
G. Gaudernack: Holder of a UV-1 vaccine patent, owns stock in Ultimovacs AS and is an employee in the same company. E.M. Inderberg: Inventor of the UV1 vaccine patent. W. Rasch: Holder owns stock in Ultimovacs AS and is an employee in the same company. J. Bjørheim: Employee at Ultimovacs AS. All other authors have declared no conflicts of interest.