Vemurafenib Plus Cobimetinib in Advanced or Metastatic Melanoma Patients
Status:
Terminated
Trial end date:
2021-01-08
Target enrollment:
Participant gender:
Summary
In the BRIM-3 trial, which was conducted in patients with previously untreated advanced
melanoma harboring the BRAF V600E mutation, vemurafenib, a potent inhibitor of mutated BRAF,
was associated with prolonged overall survival (OS) and progression-free survival (PFS)
compared to dacarbazine. In the same setting, combined use of vemurafenib and cobimetinib, a
selective inhibitor of MEK, yielded a significant improvement in PFS and response rate,
compared to vemurafenib monotherapy, along with an advantage in OS, which did not cross the
pre-specified significance bounderies (COBRIM trial). In treatment-naïve patients with
mutated BRAF, both anti PD-1-based immunotherapy and BRAF-targeted agents are feasible
therapeutic options, with the former and latter agents being associated with more durable and
earlier responses, respectively.
As suggested by National Comprehensive Cancer Network (NCCN) guidelines, the use of combined
BRAF and MEK inhibitors in patients with progressive disease after immunotherapy, is also
feasible, but it is not supported by category 1 evidence, in view of the lack of studies
conducted in this setting.
The main objective of this phase II trial is to evaluate the efficacy and safety of the
combined use of vemurafenib plus cobimetinib in advanced melanoma patients who have received
first-line systemic immunotherapy for inoperable locally advanced / metastatic disease.