1101TiP - Phase II multi-centre, non randomized, open label study of nivolumab in combination with ipilimumab as first line in adults patients with metastati...

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Immunotherapy
Therapy
Presenter Antonio Rullan Iriarte
Citation Annals of Oncology (2016) 27 (6): 359-378. 10.1093/annonc/mdw378
Authors A.J. Rullan Iriarte1, S. Martín-Algarra2, L. de la Cruz Merino3, D. Rodriguez Abreu4, E. Espinosa5, A. Berrocal6, R. López Castro7, T. Curiel8, P. Luna9, A. Lorenzo10, J.M. Piulats1
  • 1Medical Oncology, Institut Catala de Oncologia, 08907 - Barcelona/ES
  • 2Medical Oncology, Clinica Universitaria de Navarra, 31008 - Pamplona/ES
  • 3Medical Oncology, Hospital Universitario Virgen Macarena, 41007 - Sevilla/ES
  • 4Medcal Oncology Service, Hospital Universitario Insular de Gran Canaria, 35016 - Las Palmas/ES
  • 5Servicio De Oncología Médica, Hospital Universitario La Paz, 28046 - Madrid/ES
  • 6Medical Oncology, Hospital General Universitario Valencia, Valencia/ES
  • 7Medical Oncology, University Hosptial de Valladolid, Valladolid/ES
  • 8Medical Oncology, Complejo Hospitalario Universitario de Santiago de Compostela SERGAS, Santiago de Compostela/ES
  • 9Medical Oncology, Hospital Universitario Son Espases, Palma de Mallorca/ES
  • 10Medical Oncology, Hospital Universitario Virgen de la Victoria, Malaga/ES

Abstract

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)

D1W1 D1W2 D1W3 D1W4 D1W5 D1W6
Nivolumab 1mg/kg + Ipilimumab 3 mg/kg Nivolumab 1mg/kg + Ipilimumab 3 mg/kg
Cycle 3 and beyond, starting week 13.
D1W1 D1W2 D1W3 D1W4 D1W5 D1W6
Nivolumab 1mg/kg Nivolumab 1mg/kg Nivolumab 1mg/kg

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.