For Healthcare Professionals Outside the US

For patients with BRAF V600 mutation–positive unresectable or metastatic melanoma

For patients with BRAF V600 mutation–positive advanced non-small cell lung cancer (NSCLC)

Tafinlar® (dabrafenib) + Mekinist® (trametinib) clinical trials

Tafinlar® (dabrafenib) + Mekinist® (trametinib) has been studied in 3 randomized studies vs BRAF inhibitor monotherapy: 2 were phase 3 trials and 1 was a phase 2 trial1-3

COMBI-v was an open-label, randomized phase 3 study that compared Tafinlar + Mekinist vs vemurafenib monotherapy1

COMBI-v phase 3 study: Tafinlar® (dabrafenib) + Mekinist® (trametinib) vs vemurafenib monotherapy


STUDY ENDPOINTS

  • Primary endpoint was OS
  • Secondary endpoints included:
    • PFS
    • ORR, DOR, and safety

Crossover was prohibited; however, at the time of the first OS analysis, the protocol was amended so that patients who were initially randomized to vemurafenib could cross over to receive Tafinlar + Mekinist because of the clear survival benefit.

COMBI-d was a double-blind, randomized phase 3 study that compared Tafinlar + Mekinist vs Tafinlar monotherapy2

 COMBI-d phase 3 study: Tafinlar® (dabrafenib) + Mekinist® (trametinib) vs Tafinlar® monotherapy

STUDY ENDPOINTS

  • Primary endpoint was PFS
  • Secondary endpoints included:
    • OS
    • ORR, DOR, safety, and pharmacokinetics

Crossover was not allowed during the course of the study in order to preserve the integrity of the OS endpoint. However, after the 2-year OS data cutoff, crossover was subsequently allowed and may confound future OS analyses.

The 220 trial (part C) was a multicenter, open-label, randomized phase 2 study that compared Tafinlar + Mekinist vs Tafinlar monotherapy3

220 trial (part C) phase 2: Tafinlar® (dabrafenib) + Mekinist® (trametinib) vs Tafinlar® monotherapy

STUDY ENDPOINTS

  • Primary endpoints for part C were PFS, ORR, DOR, safety, and the incidence of cuSCC
  • Secondary endpoints were pharmacokinetic activity and OS

BID, twice daily; cuSCC, cutaneous squamous cell carcinoma; DOR, duration of response; ECOG, Eastern Cooperative Oncology Group; ERK, extracellular signal–regulated kinase; MEK, mitogen-activated protein kinase/extracellular signal–regulated kinase; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; QD, once daily; RECIST, Response Evaluation Criteria In Solid Tumors.

References: 1. Robert C, Karaszewska B, Schachter J, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372(1):30-39. 2. Long GV, Stroyakovskiy D, Gogas H, et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet. 2015;386(9992):444-451. 3. Flaherty KT, Infante JR, Daud A, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med. 2012;367(18):1694-1703.