Phase II study of dabrafenib and trametinib following progression on BRAF inhibitor monotherapy in metastatic melanoma: Exploration of clinical and molecular predictors of response.

e20051 Background: The combination of dabrafenib (D) and trametinib (T) has demonstrated clinical responses in a subset of metastatic melanoma (MM) patients (pts) with BRAF V600 mutations after progression on BRAF inhibitor (BRAFi) monotherapy. We conducted a phase II study to identify clinical and molecular markers that predict response to D+T combination treatment in these pts. Methods: MM pts with BRAF V600 mutations that had progressed after BRAFi monotherapy were treated with D (150 mg twice daily) and T (2 mg daily). Treatment response was assessed by RECIST v1.1 every 2 cycles (8wks). Tumor samples were collected prior to starting D+T and were analyzed by next generation sequencing (NGS) for mutations, RT-PCR for BRAF splicing, and by IHC. Blood samples were collected at baseline (BL), C1D8, C1D15, C2D1, C4D1, and off-study. Level of mutant BRAF RNA in circulating tumor cells isolated with peripheral blood mononuclear cells was assessed by RT-PCR. Results: Twenty pts were evaluable for response. Th...