(EAY 131-H MATCH): Phase II Study of Dabrafenib and Trametinib in Patients with Tumors with BRAF V600E or V600K Mutations (Excluding Melanoma and Thyroid Cancer)
Description: 
Given the efficacy of dabrafenib and trametinib monotherapy, preclinical work began to explore the anti-tumor activity of the combination. Experimental data generated with a BRAF- and MEK-inhibitor administered in combination in BRAF-mutant melanoma cell lines in vitro and xenografts in vivo demonstrated the efficacy combination therapy in models of acquired dabrafenib resistance. More importantly, superior anti-tumor activity of the BRAF- and MEK-inhibitor combination as compared to each agent as monotherapy was also observed in BRAF-sensitive models [GSK1120212 and GSK2118496 Investigator¿s Brochure version 03 23-JUN-2014]. This finding was confirmed in a randomized, phase 2 study of a combination of dabrafenib and trametinib, as compared with dabrafenib alone in patients with metastatic BRAF V600E and V600K mutated melanoma. In this trial, the investigators demonstrated a longer progression free survival with the combination (9.4 vs 5.8 months), as well as less squamous skin carcinoma (7% vs 19%).17 Based on this study, the combination is now FDA approved for the treatment of V600E or V600K BRAF mutant melanoma. Recently, a double-blind, randomized, phase 3 study without crossover was published comparing the combination of dabrafenib and trametinib to dabrafenib plus placebo as first-line therapy in patients who had metastatic melanoma with BRAF V600E or V600K mutations.13 The median progression-free survival was 9.3 months in the dabrafenib¿trametinib group and 8.8 months in the dabrafenib-only group (P=0.03). The overall response rate was 67% in the dabrafenib¿trametinib group and 51% in the dabrafenib-only group (P=0.002). At 6 months, the interim overall survival rate was 93% with dabrafenib¿trametinib and 85% with dabrafenib alone (P=0.02). Available efficacy data of dabrafenib and trametinib in patients with solid tumors are listed in Table 1.
Study Number: 

NCG 275215 H

Phase: 
2
Principal Investigator: 
ClinicalTrials.Gov ID: 
NCT02465060

To inquire about participating in these studies, call 1-877-ASK-RPCI (1-877-275-7724) or e-mail askrpci@roswellpark.org.