LBA27_PR - Phase II Three-Arm Randomised Study of the Braf Inhibitor (BRAFI) Dabrafenib Alone vs Combination with Mek1/2 Inhibitor (MEKI) Trametinib in Pts with Braf V600 Mutation-Positive Metastatic Melanoma (MM)

Abstract

ABSTRACT Introduction Dabrafenib (D) combined with trametinib (T) shows enhanced activity in BRAF V600-mutated cancer cell lines and xenograft models compared with either drug alone. Preclinically, D + T delays resistance and prevents BRAFi-induced proliferative skin lesions. Safety and efficacy of D + T, were evaluated in a four-part Phase 1–2 study. Safety and efficacy from Part C, the randomised study of D + T vs D are presented. Methods BRAFV600E/K mutation-positive, MM, BRAFi and MEKi treatment-naive pts (≥ 18 yrs; ECOG PS Results Pt (n = 162) baseline characteristics were balanced across the three arms. Investigator assessed median PFS for 150/2 was 9.4 mo v 5.8 for D mono (HR 0.39, 95% CI 0.25–0.62; p Conclusions D + T provided a statistically significant and clinically meaningful improvement in PFS, RR and DoR compared to D mono in pts with BRAF V600 mutation-positive MM. The data is consistent to Part B reported with D + T. Increased incidence and severity of pyrexia and lower incidence of hyperproliferative skin lesions are observed with D + T compared to D mono. Phase 3 studies are ongoing. Disclosure G.V. Long: Has participated in advisory boards for GlaxoSmithKline, Bristol Myers Squibb and Roche. Has received research funding and honoraria from Roche. J.A. Sosman: Has received research funding from GlaxoSmithKline. J.S. Weber: Has participated in advisory boards for, and has received honoraria from, GlaxoSmithKline. K.T. Flaherty: Has acted as a data safety monitoring board member and consultant (compensated) for, and has received research funding from GlaxoSmithKline. J.R. Infante: Has participated in an advisory board for GlaxoSmithKline. O. Hamid: Has acted as a consultant (uncompensated) for GlaxoSmithKline. Has received research funding from Bristol Myers Squibb. L. Schuchter: Has participated in advisory boards for Merck and has received research funding from GlaxoSmithKline, Merck and Genentech. J.S. Cebon: Has participated in GlaxoSmithKline advisory boards, and has received research funding and honoraria from GlaxoSmithKline. I. Puzanov: Has acted as a paid consultant to GlaxoSmithKline. A.P. Algazi: Has received research funding from GlaxoSmithKline. K. Lewis: Has received research funding from GlaxoSmithKline. W. Hwu: Has acted as a compensated consultant for Merck. Has received research funding from Bristol Myers Squibb. R.F. Kefford: Has participated in an advisory board for GlaxoSmithKline. P. Sun: Is a GlaxoSmithKline employee (Statistician) and owns GlaxoSmithKline stocks and shares. S.M. Little: Is a GlaxoSmithKline employee (Clinical Development Manager) and owns GlaxoSmithKline stocks and shares. R. Gonzalez: Has acted as a consultant to, and has received research funding from, GlaxoSmithKline. K. Patel: Is a GlaxoSmithKline employee (Director, Oncology Clinical Development) and owns GlaxoSmithKline stocks and shares. K.B. Kim: Has received research funding from GlaxoSmithKline. All other authors have declared no conflicts of interest.