Sequential Combo Immuno and Target therapy (SECOMBIT) study
Research type
Research Study
Full title
A three arms prospective randomized phase II study to evaluate the best sequential approach with combo immunotherapy (ipilimumab/nivolumab) and combo target therapy (LGX818/MEK162) in patients with metastatic melanoma and BRAF mutation.
IRAS ID
227856
Contact name
Paolo Antonio Ascierto
Contact email
Sponsor organisation
Fondazione Melanoma (ONLUS)
Eudract number
2014-004842-92
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 0 months, 30 days
Research summary
Melanoma is the most serious form of skin cancer, with both incidence and mortality rate rapidly increasing worldwide, constituting a significant and growing health burden. The worldwide incidence of melanoma in 2010 was estimated at 208,251. About 80% of melanomas are detected in a localised stage, and can be surgically removed. When detected early, the 5-year survival rate is >90%; however, when melanoma is diagnosed after metastasis, the 5-year survival decreases to 15%.
Discovery of the genetic underpinnings of melanoma has uncovered potential therapy targets. Mutations in the BRAF gene lead to growth and multiplication of cancer cells and promote their survival. Treatments targeted at the BRAF gene to inhibit these processes have been effective, however, response duration has been short and development of drug resistance is a problem. There is therefore an urgent need to develop new treatment regimens to combat these problems in metastatic melanoma patients.
The primary objective is to define the best sequence of combination therapy which will improve overall survival (primary endpoint) in patients with metastatic melanoma secondary to a BRAF mutation. The study involves giving two drug combinations - LGX818 and MEK162 (combo-target therapy), and ipilimumab and nivolumab (combo-immunotherapy) - in three different sequences. Participants will be randomised to one of three treatment arms, starting with one drug combination and switching to a different combination upon disease progression. Lesions will be documented at screening and reassessed at each tumour evaluation (8-weekly during year-1, 12-weekly thereafter) according to RECIST 1.1 criteria; assessments will be by CT/MRI scans/physical examination.
Duration of participation for each subject will depend on response to, and tolerance of, study treatments. This randomised open-label study will recruit 230 subjects in ~30 European countries. Up to 18 UK participants will be recruited from two NHS sites with expertise in the disease area.REC name
London - Westminster Research Ethics Committee
REC reference
18/LO/0713
Date of REC Opinion
3 May 2018
REC opinion
Favourable Opinion