Ulixertinib in tumors with BRAF fusions, non-V600E or non-V600K BRAF mutations

Vivek Subbiah, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses a subset of results from the phase II MATCH trial (NCT02465060), evaluating genetically-directed treatments in patients with solid tumors or lymphomas that have progressed following at least one line of standard treatment. The sub-protocol looked at ulixertinib, an ERK 1/2 kinase inhibitor, in BRAF non-V600 mutation, BRAF fusion, or other BRAF aberrations across multiple cancers in a tissue agnostic manner. In the absence of specific BRAF V600E inhibitors, ERK inhibitors have shown early signals of activity across multiple tumor types in preclinical and early phase I studies. Twenty late-line patients were enrolled based on molecular analysis of cytologic samples and it was found that ulixertinib did not have significant activity in this cohort. Future directions for this study involve returning to the preclinical model to identify potential adaptive mechanisms of resistance and to identify possible combination therapies to improve the response rate. This interview took place at the American Association for Cancer Research Annual Meeting in New Orleans, LA.