Phase II multi-centre, non randomized, open label study of nivolumab in combination with ipilimumab as first line in adults patients with metastatic uveal melanoma. GEM 14-02

Background

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults (6 cases per million). Up to 35% of patients develop metastatic disease affecting primarily the liver (95%). After systemic dissemination the prognosis is poor, estimated median Overall Survival (mOS) of 6 months (m) without treatment. Efficacy of conventional chemotherapy is limited, with overall response rate round 5% and mOS 8-10 m. Trials evaluating new targeted therapies (e.g. Mek inhibitors) have failed to achieve positive results. As a result mOS of metastatic UM patients has not improved in the last 25 years. UM cells express PD-L1, and have others characteristics that suggest they could respond to immune-checkpoint blocking antibodies. Indeed our group recently reported a study of Ipilimumab 10mg/kg with promising results, mOS 10 months, 48% alive at 1y. The afore mentioned lead us to design this trial with the hypothesis that combination of Nivolumab and Ipilimumab will improve OS on these patients.

Trial design

This is a phase II, multi-center, non randomized, open label study of nivolumab combined with ipilimumab in subjects with previously untreated metastatic uveal melanoma. Patients must have histologically confirmed uveal melanoma, with progressive metastatic disease at baseline, >18y old and adequate organ function. Prior systemic treatment and autoimmune or infectious diseases are the main exclusion criteria. Dosing schedule is described in Table 1. Patients will be treated until progression, unacceptable toxicity or patient withdrawal. Selected cases will be treated beyond progression specified per protocol. Objectives: Primary Endpoint is 1 year OS. Safety, PFS according to RECIST 1.1 criteria and correlation between biomarkers and clinical results will be evaluated. Statistics: Predicted sample size is 48pts. H₀ 1yOS= 27% (pooled external data). H₁1yOS= 50%.

Cycle 1 and 2. (1 cycle = 6 weeks)

Clinical trial identification

EudraCT: 2015-004429-15. Sponsor Protocol Number: GEM-1402 NCT: NCT02626962

Legal entity responsible for the study

Grupo Español Multidisciplinar de Melanoma

Funding

Bristol-Myers-Squibb

Disclosure

All authors have declared no conflicts of interest.